ney ~ = ps mo ~j es A = cs ‘ f Determination of the Active Principles of Medicinal Plants Chemistry me M.S. a ree 2 1901 eK se a aes Tae Ce eS Se, Si ST ST ok kK OK ye" . he SE SS 8 SR I OR IS KO SK OOK OKO NZ SY Sy Re ES ie a ST STINTS EES EE SS aie Se SV + ~ . * re SS ee ee | ak SS — + yO ENE SS SIS SS SOK PISS a a SE NN NS SS SEO OR ee A Oe ee ee SS a, Sh ST. SN he he Ok Ook OK OKO VE SESE SES OS SOS Kk Ok OK . ONS SESE SE SIO IS a oa ESSAI ESI OR ae 7 > + * | = : " WV NZ Sy PPE EEE EEEESEES EHS N AX a a i, ie i & earning and Labor. ) a NY y WA Wi, . OS OR : LIBRARY MISTI * a . 4. y " oF THE t — VISES ESS 4 University of Illinois. 3. i i i * i ah a RY i CLASS BOOK. VOLUME. 4 ae > x | she | > @ a B KO RIN VISES ESS ND ONAN A IRI Nv he + + | 7 —— * A f i Accession No. «0... eee a kK * Hs + Kk e) We. 3 RY YIN SPEEREEEESETSECCSL fe DETERMINATION OF THE ACTIVE PRINCIPLES OF MEDICINAL PLANTS. ap BY CHARLES ALBERT WALTER, B. S., Ph. C. FHESIS POR. [HEsDEGREEJOF MASTER,OF SCIENCE IN, THE GRADUATE SCHOOL. UNIVERSITY OF ILLINOIS, I9Ol. sr} ¢ WW LLcL mio wit eas | Pus Vitl an ae & . may pe at | ¢ Nat 1h) = aL Vek Ta 2 { GDts Af THe ela "Lie aun OSE & sinta + + aN c ~~ Physician has al = + + (> tT qa -- 7 Te Ne) aie ©) ” L ) al me es = will vov a + reo* a1 joa wnrc LO Bee GL sg Lm € ‘ VT Ox v \ L ~ \ ° i 4 F = ' re SS) € u cu 11 US | 5 | 9 ak Aat a) tah & As s J Ce bi st sil rer a) ~ ayn ye Whe ( *] ‘| . whe er + y) 4 | a a) c o c oO as | ~ ) 1 Cy) ¥? 7 - ‘ ze a | ‘ yo fom | - ad J 4 + &* vO Int J u i OS possess any value ~ ~ as) @) gall <<“ J ut ( U ate| map| mo t RPaASAS aconite vy the t Yr¢ 1 oy) 7 Z © f - ) _ L gquantit ave « 7? ¢ yc 7 ja morelwv ww 4 \ s. a ~ ot Deki, oe 1) > , O71 BUD CG A pe ls NRANOAYRPATAN 3 tAL Wh Cu CA sks ~+ O ~ u og ele aks ec J , 7. « Hn 1% CALt MAY 7 4 Cy U KW L Fog a ie em a+ ~ 147 a OST So weit es c rhe - VT +hig , ery uss er - yar 7 ae ; HoOenes UDG tac oa aw 14iz ; + CAY CAL _—_ > f al + + ou co « € Ow + + . 9 = L 5 + + ec 7 4 oT + c re 4 ry 4 aly poenac ote CA 2 , @ 2 Va a ) ac ) ‘ \ 4 * ‘ 7] ‘ ca “ToL ¢ ] A LU | Cc er ) 5 Ver 45 ww . 4 a 1 av rel >t ‘ ale! Nt i V¢ oy A entir: THES .. ( rf ) p r noc ay) YHvat 41 QA19 Cus it oan & ia A. ’ 4 4 ma bs. 1G Ctl " ) ‘ \ - r nMNac © Oo] L 4 - aS {T- ae aes Al sors ( ) { ’ 4 c a S + ECU e LS c annt new, ¢ anowtwn = 4 fT, ° ine c ‘7 rans .C a ’ an f ( +y oe 4 , enc =a One €f ina ane z yee ee Pe es hee ybuLe OL bl 7 2 a“ < 4 + - ? a ET ees, i 6 \ J i Le a 1 LL ‘ ‘ + a VY { 2 Ca. \ : ai . 2a f hes e) ) Li= e > as 4 + - yi ( ‘ ° LIISIl, or > % t CRCOMD AI Lae ? > . 1 4 >" 4 jf aho 3 r ( @ © | ° i AiLOLOE 4 . e s hn 4. ) Vv 4 * ee | 7 <€ 5 < ht a a LU Aw A ° ¢ ~RmoO114 1 ao 8 gt! Cab i= + <7 i e 7 | ga itje LL a is x. ‘ ° s recently bee ace L ) A é i \ . ( € act { Li LL F J u 9 LlOU e4Ane ec jt u ar) N xu - tain ot \ " , } r P , , pos 1B} i é é 9 sro¢er e ( Pat eT nia i 9 L / ’ iy j aNd sey more iene t=) U a ne Our my They that line of worke cq “ ~~ » - aor we L TO) runs S1x oY “ ( a1) ( m1 a re} > LNe orm Lo » —T ‘ Lsanwna) ) T CO if ( y tT) a > € unNnyrie . | ) } 7 +» } ( should be obtained, 1 Ce 6. Various sizes of giass per Those regular] Si r TO! + * ~ a ~ . Tee recy hayes b i from lee inche: ° é > Xe c 2 ¢ Ole f On a = a Cc te n yt | ( Ba) . ‘ QT ( ( C) . y | \ a 9 Ye J W& ad v © = ‘ | + n ‘ou Ot Ss LY WY Ul & VFO ] Pe £ Yr al ‘" 4 b ‘ .7 4 5 1O + PIO OD cA \ w CAL t 4‘ des al 4 is pl ‘ ~ 4 4 an 4 ann with Uv ad C U cu \ \ On WlLtn a | nT Boat > nal: P , c) 2 ; i o 1TeCu Ui Le AN CALL 4 cu mm lac Dhyire- i ant 4 ‘7 te Lees o r Jj Ma AU U Lt) dar Or SLre Loum 3 O7 Surable CUT Standardization ires any thing at all, . 3m scurate e Ment. t has been 141 . Sar aaaotiin informe a, 2S anoaretus , ] rc ‘ re 4 a fava t| ¢ mo aay ; L ( hy ; nm Ort Nk CULDRe Wranc3 es oi me , . Ao A PTITTS bs A o = = + Be tor: Bhe ; sr assai perati ann 4 pea) | "+ c lec ’ atus is q ed. rt 1 - A 4 + at . ar Nt OSE es the ordinary ute Ss 1 LE Se A ew HECTESB) :O svec! ml wA e Wane W IAC, i } rea ana wil nere o0@ aescrlbde . eee -lieasuring pipette 4 vee ‘ . ) LUME yi Lid OC « © 4 %G > lal ‘a ata! by ( ( ° ¥ CeCe > ° e979 ari - Nae ° Ne ie) ae e t, t, € rs U ‘ + LO wated to tentns € Ot ne ; ano 417 - + 4 -_ ettes refully testea as € © w4 ~y ae | eo) ee nes f woe MEasurL ly L 1 Cis 4 \ / D1 f) f oor ROM ; )» sd 9 YIU» L J} )9 IU, vo 4 ; ( P * : sie Ve . : ° j S----ror tne volume - ( bDUPYETtTES are PFReQulLred. Coe ¢ m ae t erviceables; alSO 2D Cec. Lhe .Y 1 >} ‘ ‘ ' f c ‘ e Ray he GQ as a ilu , +4 SCH Y 4 . . WH: 5 eaniw +n of WE f1tTNOUT e it 18 MeL net 3¢ LVE Prom ~ *t c OT NE ii c —— * { ts ot Gy'T* ( Lin 9 qi re S to r S 4 n SO ) t ~ *oOOlk ; — ODA on 4 Sa v Ls ng els----No piece of eC oO c 1 ( » Perf) tog es , ) 2S. 2a ~ 9 i " ahle = sO CAN, } Ws Jad ‘<€ War S 4 C at a ae . r¢ 4 au + ‘ Ulla. u O Ed “~ : < AY r 7 K are | ‘ ( sho 9 ofl jet ‘ ( ¢ _ * 9 . \ 7 ° \ OT 7 4 Cou K L L > r ° yO ey ae ea FEEL 2 ) mebe eo ‘ ‘ wu °9 ri s [ < ? © +) +7 OR Ww SAO MS ° Ul avr ° , “ OeC 4 ry 4 4 2 7 > + ¢ c 7 ‘ c * . . { at I uUNnyr ws) OT Dee 1 © ( LO CO i l OY) ot whi! ilteringe A funnel about 4-6 inches Brn - A 8. inpararus for hot repercolation. For ‘the apid ex- > ~ -£? ‘ - WeA\tRre We rlacii es 9 LYaIseS Ab? THe to] ( | ‘. aoe BF ladesecde/ 5 ne Si ) THtoS Ge aphahal S Lu . rij Sia’s ) Cc l aT + OY A TO whic i+ ’ Yr ¢ S ve A. j i \) S ( I id from which it 1S to ex t | ‘, T Mo wiki th fann should rer five places Lith @ Lise, so cave bs Ot several. ALFTectilons. lt may happen Lat TECLOLG rent L >) ide May remain unal ssolvea 4 allkkslaia nn + “2 the acid alkealoidal solutio solv Lo remove any C luble in the solvent . alkaline by a few drops ar el ye a SOLV CLL’ attache G ana \ Leak - a> . | 2 % no yv) q The alkaloid can be in yr three hours, with a process that Af S prac tic al. 143 nt different ex Ww, If oform, a j ‘ent form Here, I take a test tub and substituting this f paratus. The liquid, the test tube through v of the tube and slowl es the bend and flows o case, the Liquid 1 upon he chioro ~~ ever fets outs some chilorofor first be nvlaced kaloidal s &tLOMrs« OL yr © pi 5 _ om } Can oO LS - ) L Lota ( rf C7 ¢ e t> Y Gs 10 BLED , é SOLVvVen ( mm" A ea LO tC } ot ( ) { . : () ¢ Py 4- } a 4 > c 5 | a aUCQ a LK! O LO i ( df »f Whi ¢ JL sel i LIPIAal A UMA yy 1 is asned ~tnorougn.nr Los ( ne matter or otner materiée s0= , 8 eT : =o a ne Al “> 3 do 1 LAGULiag 168 tnen renaereda Lal! es ammonia, a new flask and fres: ~~) de on Be 7 wes a} } 7 ec LOL Ladavead ALKALO a WABNECA OUve 4 . yous rm Ma + : . tracted verv completely in tw + imum amount of solvent and e 2 R ‘ | eax ae me | UuGoMa tLCe CS 1GeC5 » '& Dg = eS e conducted at c nC@e bebe ADDE ile The me ef in alk Kalo ida | works motor a Sl" = a a Warner m0 0} Gis nary ingenuity will devise a le «é= «4 ert + ; \ 1 ory nN . > ) | ¥ . @sarea res ALG, .10 Aid Gepe 1d in on the LOCatlLens ‘77 TaTATM REAG HN T S - 12. Prollins mixture, mLoyed for the extraction of alkaloids from crude drugse a) 1 FORMULA, Concentrated Ether- . ~----325 Ce Ce Alcohol--- ————-= ----25 ©, @, a . . ny oc, 4 ” a , ~w4 > . stronger water of amnonia--- O Ce Ce Ln tne alconol and water ot ammonia and add 0 le etner, Bigs. Prolline id modified; usea for j waicn are snail ing SOL oe 271 € Une! P in extraction iro crude. .adrugse = FORMULA. Concentrated Ether---- PEO Ce Cs Chlorororm- oe an ~ 80 Gq Gi Do con's ).—~~~-~ . ‘ rte Ce’ Cy strong: f Wa el * | | wale La - al si sat he og 7 -1LO Ce Ce 14—e Mayer'*s sol on of Potassium Mercuric I: ¥ used for the detection and volwnéric estima on oO noe 00 ib? @ L Litre, aAaSBLUM LOGIGE Iodine in Qualitative Prescot LLronine ae Lutio LOoIas wie yc great y1elas -S.. | SOLVE 5 TOlumetric odide, n anda a wid a Wd cu To oe Lil tie oe —- oO > | L ud , t a \ f- e © a ba, Xs VV ke a ee y oLume IAG aves OFLOS= rs ake ae / t ow V ‘ Cn f ; =) ¢ > pVileiim mh m A i \ \ > > wD \ . Ab CUS d LC A LA 2 2 hiAwtLiWtle S ary 17 ! >) ) > 5 ( . wi Cousi8 * Bi 4 ‘ FeQulds ca, J 1o Trine | oa P 7 bm ¢ ] QLlSSOLV IIe Jf GiG@ OJ PTL ot.) Lct . 7 ‘a ra a } > -\ \e } ¢ a £4 < () { ws + i* Od CONCeILY Lv ee l¢é L Gf ~ ) 45 COLAs eri ie 3g a0 +4 } 7 5 . < 7] vy’ é 4 - ss P Gr ie Acia 301 1 22tO0N LLC t>— res SL 4 $f Or a. | , + 4. * LUALES « a0 4 aye ¢ Dy Sart ee ae A feral, wee ee: da Eo ah eee nee tannic Acid solution which unites with tne alka TasAnAa ta fary 0a : ee Ee ys ans mvnean:. al Eas mn xxy PP. ee es t+GOLG68 40. Lo0rm gres ish=- yellow er greenish-nprown colLorea pre , es. . Clip. LaELES»s “a2 nT _ ee >> ae oe i ea oe ar ee any! 1 vO § . noe Mercuric Chloride solution vields white precipi- be “ie 3 Sie hy fe = 0 ee as ~ ce cee mee Sel Ea At areas je i 2 tates with the alkaloids Aen are now very sparingly soi- =. a ae ~ Pe | - 1 . - 4 — . . + ¢ ubles Rt wYnP sesse 2s TAALUE ahh VIL i does LOU prec Lid Wer 7. .f « Pe armmonical salts. oA Tt, - , 2 is ir i ace at 1 ’ el ti cae ed ve Kathe Ste § na; Wh glo LZ ean SOLULLON OL LlOoaLnNne GQlssoLvea Ly al water with iedide of potassium to be anou strength (12.653 gms. of free iodine in 1000 c, c, Thi solution may be made as the volumetric test solution or jedine of the Us. Se Pe, and usea with the exact decinormal factor of iodine, if preferec, 25 A solutien of sodiun thiosulohate,. of ahout decine ermal strenzth, standardized * mage Lis 9 Ca ©6O a KNOWN PaLLO 4 7 Lier Gine solution, The volumetric test solution Of sodium Tair Oossulphate of the U,. S. P., may be used. 26@ the starch test*solution of the Us Se Pe 2% Chinoidine Iodosulphate, employed by Dr. De Vrij for the est Lon of quinine. Heat together on a water ba Wd, one ie LI we or chi sV idine A d. 2 VO parts > en @ Ls Decant the clear solution and agitate with an excess of dilute sulphuric acid. To the hes solution contained in @ vessel, add slowly with contin iS stirring a solution of one part of iodine and two ated ‘of votassium iodide in fifty parts of water. The precipitate of Chinoidine iodo- sulphate subsides on warning, and it aed to he washed repear- edly with water of decantation, Dissolve one part of this precipitate in six parts of strong alcohol by aid of «a water bath, heat and allow the solution to cool. Decant from the deposit evaporate and dissolve the residue in rnt of celd alcohol to++¥ ms Pate\A Chale d- 28. For the Alkalimetric estimation of alkaloids, we should have normal and decinormal solutions of sulphuric acid. Hydrochloric acid and potassium or sodium hydrate n andn are frequently used in delicate titrations but 25 166 they can be prepared as required. 29. Indicators: Various indicators are employed in alkaloidal assay work, chief among them being, Brazil wood, Cochineal, Methyi, Orange, Haematoxylin and Phenalthalein. Iodeosin in another indicator, regarded by some of super- ior merit. General Methods of Assay of Crude Drugs. 30. Selection and preparation of the sample, It is necessary in the first instance to secure a fair average sample of the drug. A handful of the drug should be taken from several parts of the package or bale in order to insure such an average. If the drug consists of large pieces, valuable in quality, select a few representative pieces, Take from each of these, a good section and re- duce all of them to a coarse powder, Mix well and take a smali quantity, about 50-60 grammes and reduce it all to a powder of desired fineness. In general, the finer the powder the better, as the extraction is much quicker and more perfect. The average fineness desired is No, 60 to 80, When the drug consists of seeds, leaves, etc., nearly uniform in quality, it suffices to reduce to a coarse pow- der, at first about 300 to 350 grammes, taken from dif- ferent parts of the package, as already explained, and then reduce 50 grammes to the uniform powder, 31. If the drug requires to be dried before grinding, the loss in weight during the operation must be noted and the requisite correction made in the results. Of course such a correction could not be exact but only approxima- tive, as some drugs are hygroscopic, gaining weight in damp weather, and losing again during dry weather, The only value of an assay of the drug, should be when the drug is in the condition to be used, as it may vary as much as 5% in moisture at different times; The only ideal and true method is to assay the dried drug and thus give for a basis, the thoroughly dried drug as a positive invariable quantity. In practice, we deal with the variable, hygrose- copic drug and so must be content with practical not ideal results, Of course, in case of a drug not to be used at once, particularly if it is to go into the market with a guaranteed assay, the moisture of the drug should be de- termined and reported as an essential part of the assay. 32. Methods for exhausting the drug:- The methods for exhausting of the drugs group themselves into four processes, each of which may have, in a particular instanc¢ its advantages. a, The drug in No. 60-80 powder is placed in a bottle or flask, with a measured or weighed quantity of the chose en menstrum sufficient to insure eomplete exhaustion, at least, eight or ten times the weight of the drug, securely corked, and allowed to macerate therein with frequent or continuous agitation for several hours, at least; and in some cases, from one to two days. Any mechanical shaking device is very convenient as te flasks can he fastened therein and removed when operation or extraction is deemed complete, This method is not the best for all, as in major- ity of cases the extraction is not complete. Besides, it mn a ~ 4 takes longer time than other methods. De Percolation:=- The prin¢iple of Percolation is as follows:- When a powder placed in a cylindrical ves- sel, with a porous diaphragm below, is treated from above with a liquid capable of dissolving a portion of its sub- stance, that portion of the fluid first in contact, in passing downward, exercises its solvent power on the suc-+ cessive layers of the powder until saturated, and is im- pelled downward by the compelled force of its own gravity, and that of the column of liquid, above it, minus the cap- illary force with which the powder tends to retain it. The details of the process a@re hardly necessary here, as they are too long to give and, besides, every chemist and pharmacist is well acquainted with the process, (However, for details, consult Remington's Practice Pharmacy, srd Ed, Pp. 262-282). This process, when properly conducted, as- sures a more complete exhaustion of the drug. The opera- tion, however, comsumes more of the operator's time and requires more attention. Ce Boiling, with several successive portions of the chosen solvent, This requires far moretime than some of the other methods and besides, heat sometimes affects parts of the alkaloids. CG. Hot Repercolation:- This is by far the neatest and most effecient means of extraction, The Soxhlet Extrat- tion apparatus (par.8), is the best form. It enables us %o use a minimum amount of solvant and very little time to watch it and the extraction is always complete, When once set in operation, the action is authentic, so that the method after all is ecconomical of time, particularly where the assaying is required to be made frequently. 33. Choice of Solvents:- The choice of solvents de- pends upon the nature of the drug under examinations In the majority of cases the active prin¢iple desired is an alkaloid, present in the form of salt soluble in water or in alcohol, Here, again, we find trouble. If we extract with water, we extract gums, starchy matter and various constituents which hinder our subsequent work, While al- cohol is to be preferred, it must be remembered that it extracts resins of various kinds, coloring matters and a great deal of inert matter, Nevertheless, alcohol is the better solvent and the stronger the alcohol, the better the result. One thing against it is that it does not penetrate the drug as well as water, so in some cases, it is advant- ageous to moisten the drug with water, pack it and then extract with the alcohol, The immiscible solvents are very good for extracting the alkaloids from various drugs and do not extract much inert matter, Acidulated water and acid- ulated alcohol are sometimes emploved, 34, BE. Landin uses kerosene as a solvent and claims good results, especially in the extraction of the alkaloids of Cincona Bark. 35. Another method consists in mixing the drug with milk of lime, magnesia or sodium carbonate, thoroughly mois tening it an@ then drying. Then, extracting with alcohol or wood soirit to exhaustion, This method works very well with some drugs, especially with those heavy in alkaloids. It does not extract much inert matter and the alkaloids are easily separated from the residue in a state of medium puri ty. The method is, however, open to the following object- The object some the employment c rarie These different inixtur th See . alkaloids not bei tuents oj tion, aided ten all + s le =\) Laken out of th 4. u 4 u hat _ yy O tV up ‘che a to leave 4 py ti fter added free u iA rene? u anot volume , part « ~~ * L. Yeu t Bi other considered desired ee : 4. ExXnNaust ~ t ier , QY Ole a measured ] quantity of water oi a - } ; in ) f tne m C< va i "ou reir Ve 00uUurs Ls necessary. + + 7) ~~ i ) , © SsOLVeNnt Wait Lt JiL { eS Gr 0 and eer on 5 ’ | ok. sto Dperead to make up a vloume of Cam pe poured evident, however, when | ere G. Aa 30 that ther Lom Waat. Li : drug used. at « tae pest and then CL. C estimate the the Ee quire i time tO the mixture t to lump and collect in we Filter the solutio alka. tO 2 MaV 7e€ es drive off the oi modific i Oor Velo al Oe &Tanoyrat ALCL AUG 1 5 ; = 7 ~~ Avil AYU 40S Ula > ~ aw > ~ — JAM LL « AL Syi.cl Jz - A im mM Coe ins ~iImrereame wiii ctl SOULE ; oo . ta . — ewsn0r= CY avs A = ie Sar : a ~~ AS ~ > oes = ; i - — =< Ye > ~< - _— : _ - > 7) ot . DONaLSe 1 , ere i : ec ; _— « . ~~» v With sSuLp a, ® off, the liquid rendered al Lt rit suastic so shak out with ether at once. 42. The foregoin the 3t methods i Le previous to 1, when Pr (5) proposed an improved method for tue assaj md from this, egrad- ually evolved the man ethods rv USE « 43 "ne iet ho ) Dié I 1 ] Cit. Used by some chemists in German) ists 1 the drug with calciun te and a little water, dz 7, powdering and extract ot repercolation wi ether, #he residue of impure id ining on evaporatit Che ether, is « - solved in alcohol itrate t sentinormal hydrochloric acid. 14, Method of Schv (6)s- Te rams of the fineles cut ar ( aconite, belladonna. etc.) are put into a flask wit. OP GeCe OF 1 ig bai J Gar AL1UtEe sulphuric acid, securel} L t m e over night, occasi bi keslis i Che rxti g. ah LS Ge allowed to cool, strained, the re lue pre ed. Of. the strained liquid. 160 c.c. corresponding with 8 grams of the drug, are evi sd on th te} nepal mstant stir- ring, at at ture of abo ercre C. ; ed to apout 20 This solution is the red Jj . thin stream, inte 380 c.c. oO tron CO tne volume made up to 1 @.¢.5 the mixturs ren and rest until the sedime ts 1 LtGtiw: « G@ alcoholic solution, < 6c. @qual ti ? lrug, are measured out 2vapora OO C.sCe d toa separatory funnel, 1 c.c. < wate Ce of mixture : yrofon = 1 ether 5 volumes, added, the whole shaken together ¢ sid em ionizing, for some time and allowe CC “ate. ‘inally 2h Cee. or ether chloroform mixtur "ed ou raporat na capsule and titrate t ent ma] id. usi 7 neal ac on a ammonia = Cc. Ce With t i 3 = tel Sam ee fe oe ana nack ina liniavure +4 - ow oe the barrel of a dle te cotton is placed another vortion ahove it. slow vercolation with e Make sure that the drug : ” . ee ~ ae ¢ tn“ few arovns oF L. (=) s ~ ~ drov of centinormal sult reagent. A Yr? AAT IIMA 1 Vy ¢ “O « ntvrocuce une oc normailsulonuric acia a | sen ry Qaraw O17. Wash hp att ” Yonrers | Arvo 4 ~ L\ ww VIA A ww V 74 ek adding this to the acid solution in a second ser —st wri = — Te 4 . - A S80Qa ana S8SAAKE Ou | WiLL 7 Ie Nay © filtered out; filtrate by Ms and colori ng &! t After standing some tin treated hy one of the fo assium cvani a Lit she emulsion produced cil and out with ether, (2) 1 ' } , oh ci aae at S dh digested in a flask wit! « after which the alkeloid (1). The second process vreference, Liquid al} claim, cannot well be s ; 4 4-3 nf ¢ re A ala oa UNBaAtLIBLAaActory 42180 as phuric acid, Reduce % 1 time assay, use rlrom nNerco.a percolator = = al ar) ® CANA or Th | coat , < om alkKaLolas are reagent , vay ve matte Cie ore * Lov in two f 0 7. UGI GR if ne agagivi1o) Lin Wil u, The drug CLEA neing rea CCaved 80 NO wae Ys denending spendin, am l on O aaa LM Marsrer? SVE i ; rea Y! S114 se in + \y iors e Dt wl. & | Oy y* Ve] ‘7 Kok LAVA PaYs t ; f I1re ry ¥? ; v) , 1 © cou A gh OG Vo Ol soil 1n1 . . , 4" y ‘ = a grammes or water or amnonié a wo ] Tircorous.l ‘ oneat tne powaere 4 + + “ ro) a) = . m0 istened, pouAaKEeE OCC asiona ada a QGuanvivy O32 4- Ta es Al wae Aer ay? + P : the arus YNOWGECY LO age.u tinate 11¢ cranes - a) ole SJ =» 4 cu AANFID y GYrug e [% frequently happens he obtained. In such a 2 aS @ Gare be taken to avoid lose the quanti y Zt Lit rep + 72 4G + ie 1 ey or aon —, : Fe a a aravor ana wasn out tne alix adrochic YA acid nre respectively. mi is removea nv %. v rendering alkal ammoniae Three washings shoul he conducted . ether mixture le Iiys 4 ime ae fore renderin iids alkalines in: aid about LOO -cis. e of the solve USCUe The fluid is removea 4 tared Hrlemeve) eal + 200 Cy Ce Capacity, - vent recovered llation, and the vapors of et] na chloroform removed from the flask by a light current of ai from a bellows, the flask dried to constant weight an yveight takene The alkaloid is generally quite pure, Wy for ety, after ighing, it may be titrated with stan- dard acid, Digeelve.in 5 to LO Ge Ce of neu tL absolute alcohol, add water to the begin: ing oj urpidity, naitia Qrovus Of haema OKAY LL 1Naaic r, ana JinaLiy i folk a purevee n or n> hydrechloric acic untid the color changes. TO ea — ie - a ’ on \ “ - a om ’ r a?) NA L.noen ’ calcula vw UIE 1 1aN Tw 2 A Oe @aALKALOAaG YNres i Ve (38) 5O.™ In case oi ar iS Jik ergow ana nux vor ica > ii contain a considerable quantity of oil, it is advisable to treat the arug W ith ether | vw nNercolLa Lor IQ] ACE | la to extract the alkaloide The ether may, by this previous washing, extract notable the extract should ulated water, which is then found to pe quant ALWAYS De Was presenv, 16 must pb alkaloid extracted 2 Lt VObY 2 and added to the quantity of sequent assay process. 51. Method of K, Schwicke) powdered drug are digested in mixture (Conc*t ammonia wate CeCe, Biher 920 Ce Ce), for For the form of agitator with water to or waver i158 AAGLErF Dur ie Ose ; ULLE ala BdVAaANvAge , a UL aQaQaea eer: tne SRRNOR, (5 Ge @4 OF LO | Ee ramne Od. LILES arug place 8 a Ce of distilled water an phuric acid 2.5%, and set asic yermitotin u1e@ aAaLCONoOL ana et! ~ run bv powe! 6 L5 ae 50% CWELVE an) a ae , - a — + pv Le n3C 6 ere i. S - ~ Lee ] les or the alkal hed and shaxen vw ea ior aLKalOolads PeMmoveQa ps VIlS U a ath \)3- [went O Ce Ce OL a weal LO Ce _ Ce 9 Alec b] , ~ . serviceable thi m 1 Lne aris heginning of t1LONs fluid, correspo a shai low glass £64 0.8m Cevel ai in a moderately > LOOT se 1ours SNakKing oid ; nence Lt acia- BUuat Mevnoea in the sub- x &> k ProLiiins Ae) Lda? abe iTrequenwvsay ng Ls 9 OTL moLtstenea mpmeravso@n >] ott ow One eax nding to ressel ,aadd LLUGCS SuUs= Varm place, Sil ai We ght Aas ae Oe ileal St > ee via Sma. ing OarvurletLle Oy J1@ SiIiGesS O1 i Q Ls ) Ld € Pe ae -, or : . n 4 } . LAD = 4 4 a VILS AA KL C QQ Of Lf 7 ©) PU LIAL LOSI r) sL Le aAacLlLautsa vec BUCTL a . ie Ty Se i me 2 ‘ done a c LOC @aclia soL.uvcion is FTIOW 2 €r eg ster Os I eh Cry At AL «dd = ver Nto a senaratvoryvy funn or prezeral Ly LNGO &@ pers orauoy - ., “& m7 tai : —_ , 4 1 we ‘ ‘ ras} 1 (See oa! i). AL6Q LS ereavea a s + ad 24 P type al ) Rite Cy Ob ¢ VALCN 1s agi OVW 1 os « 4 1 ~ ea yO evavorawve } Oe} sea LU yu L “or Os) bt > wae ae m1 ca + he las c o & Lter Q42hna a@aacké ah LD Led, | pe ff Cepeda , ; } en lf ane ed once more if covered from the ana the approoria be meu OG S bli z pr & Ca ical reas AD TT = . 7 Ze Use or;- In- troduce into the perforator (see pa he acid soluti< oy eae ‘ 1 7 aL rom WOIACH vsLe i. | oe XA er ae si ais ey: et Nan ae + os ae re ; 4 SM0u.La now eoccuny tne exv~ractor more wnan At.- wea Li Om | - Pot . y On 4 it be a2 or V er VV wae € ri LC LY Le el er | — ee . 4 at a a P 1 oy . Ei ~ 4 ~.,) = 4CiQ SOLUGLON in tne perioravor, enougn ammonia or preirer- | - ~ + ot . ¥ y . ; 4 sn < 4 he “ Q@aoLly7y soaium ¢ Onave tO renaey NE ALGAULIA GAL1StCIANCL Jee + OA oe ae ~ a. a © ‘ . . } } l 4 Kad Lne yeconnec. € waravus LEAL d oO he c " 42S OC1OI@s trom two Terv esc rery Aare iF L0n la" vy ace ly seen. atus ada 5) react1lon , ACLAULATGI 24 1 « “yg " lan eo — S101" YOauce a t LUV le - a . - Jt ane 2 1? « ne ~~ * de “L, n b TA ~ sw Finall.; ; transier the. ether in rinse the ether which remained and wnich is easily poured off add this washing of flask orate the dryness, dry u verified esi : - . XA r) iJ G i va > ting with standard acid nt \y f > of x L Cz Os Anne, ww ] | on Q =) Ly Og - cy ok ‘ += 3 ome VT QuULOMAaAVILCE™ Si i a mm ea peel Oe Dee wrk 7 } s 2 otner lavnors. sne extraction of alkaloids plished with a minimum amount of costl 30 55 Method of ala We Llovd (10) :- To examine a dr AP, . - - qualitatively for alkaloids. Perco! he powdered ground drug with the avprovriate sol ir, ssermecpreper menstruum is unknown, with various so ts, alcoho) } ydro-alcohol, and use the percolates, as directed in (56). Tt will be best to abstract the iron magma first with chior- ororm, as herein suggested, and then with sulphuric ether, evaporating the Liquids separately and treating the residues severally with chloroform, as later directed, Ef eit is mI a & oe = is dee ™ oe a 7 - ~s a a - * : " 5 + 5 - desirable to obtain the alkaloid in considerable a 1OUnT, after demonstrating the presence of an alkaloid ; ne perco- es moantr 1 Anna = ane Ls Rae a act aA a ae acs ’ eh ain al = ~ Rw late may oe concentrated Y evaporavion and used in increas- ed DF _— tien; OUT W1tn Many evanescent alkaloids », as Nere after. described le = —_ a “ eo Pe Y niga _ : = | erat lon. Llis. ME@EvLAOa ) Py OL @ Liovd SLavtes ’ ives exce...le 6 “14 os ‘ | . Na n Sy tale tier) nH 7 DQ 1 797 f | 7 4 results ANG, OY means of whic Ll, 2€ NaS FOUND alKaLolas plants that heretofore failed to yield then, 16, Assay of “ogres ate or Fluid extractic'! Pour 5 cd. Ge Of the fluid into a t Lal @A0OUG ONE YVAN Capac 1 oy ce of a stiff magma, by me: mixture of equal parts hon= ate of sodium, Exhaust this Magma ov Uristuration wi 20 Cy Ce chloroform, decant the chloroform and repeat the washings three times with successive portions y each of 10 Cg Ce Chloroform, decanting them severally with ord inary Care » 1106 t alkaloids (of fluid extracts ) ror whic! this me- thod is comnended), may usually be extracted by a skillful manipulator by means of two of the portions of chloroform; NUG tn orae r vO Guara against imperiect ork, Lour washings are directe cd. ana ~ pains muss DE vawxen tO periorm tne washings viorougnily if the examination be quantitative. In some CaBes, the amount of chleroferm may be increased to advan- TAges Wi th cinchona, Lor exXar IpLe, the faetor mus » ne in- creased or she chloroform washings extended, because of the Slig. Lt solu biLats Od Cinchoninegs Ti mil ¢é lkaloia is now sG duble in chioreform, and is soluble in ether, use that sol- vent instead, e&1a proceea, as neretofore directiede le This treatment will liberate the alkaloid from its CG Olmo ination > ena Pr ae tical.) vransier it to the cli Loroetorm together with the fats » Various resinous bodies and most of the chlorophvil, Tannates, mineral salts, most vereta- ble acids and tg airy matters are left in the residue, If the iron riagmsé does not separate cleariy when triturated with the chloroform so. that the chloroform is transp wraces of it pass into the chloroforate alkaloidal solution. This is (excepting guarana), immaterial, however, as the subsequent manipulation separates it completely. (In case of Guarane, the residue obtained at this stage is practically pure caffe ine. Hxpress its weight in grammes and muiltipl3 by 20 to get the per centage). 58, Notes 1 on Lloyd's method;- The operator must diligently wash all parts of the magma with the chloroform which can be readily, effectually and quickly accomplished by ordinary care and the use of atula in scraping the sides of the mortar. The spatula should he about ; r- @ . & Now again will curve easily and hug the sides of the mortar. Ordi- nary, blunt, stif: SPSbULAS are cumbersome and imp? Le. After each port Lon Of chioroform has been decanted and, before the succeeding portion is added, the magna should be scraped into the bottom of the mortar. If thas part of the process is properly accomplished, the Loic to the limit of error in manipulation, will have ferred from the magma to the chloroform, and the formation 1 our LY! OLAAS VAN slender ana sv e a0 tT0a% 1LLE J of emulsions avoided. If the wa becomes friable when the first portion of chloroform added, then mixes wi and absorbs the chloroform (as be the case if the fluk extract be strongly alcoholic), to the mixture, after the preliminary trituration ae: CO Oo Co Cy Water, 0} better, the necessary quantit; mixture of equal parts glucose and water, being careful use as little as possi- ble. The magma will then separate sharply from the chlor- form (as it should), thus favori the approximate absrac- tion of the alkaloid and preventing any considerable amou of chlerofon ffom rer geen in the magma, end holding its proportion of alkaloi therein, The mortar should be capacs ious, oat “ene Flat porcelain style, all porcelain pestle, and possessed of a good Lips it seems that some well informed pinnate are lamentably awkward in exclusivel pharmacal manipulations; end it appears as though the skill ed use of the mortar and pestile has become to be practi- sm & lost art with some talented assayists. It may be dn he = we ans wv , + « . rs 9 remarked that beginners in assayin a Mortar, RO Wotea on the 2nd ctens- GCraduallw i Pe ree JIV~e YOUUGCHS dIl vi lL AHQA HPHLEpPs rFIAGQU CLL § pou ILS al OF ©& 0 + ou ath anne yloait4 inte 27) > YOR * TY ‘ ‘ Y going chloro! Orm SOLULLON into an evaporaving a5 1! ( J c flask connected with a condenser, if it is proposed to re- cover the chloroform), on a water or steam bat continuing to add the chloréform solution «as the solution evaporates. It is not best to attempt too great economy in assay work but prefer to evaporate the chloroform at as low a temper- &2vLUre as possible, in an open dish. it is always best t< UusSe G& f Lat=-bot tomed evavnore i ae ap being to spread the alkaloidal residue in an even thin film over the bottom of the flask or dish, so that ween the acid water subseauently added need not be in large amount, it} will thoroughly permeate it and extract the al- kaloid. If a round bottomed evaporator is used, the resié 3 a ery mn ee rosr ha *a a ae re, See [en oe Se , ane ue in some Cases Me.) be too thick for absolute extraction. > és = a ane ‘ ] . 5 4 = a a a ea 60, Notes on 4rd Sten; - Then az Vel le CnLorol orn - b } x Ors se, + 7 Ay . + Lh wen 4 as¢ ar at . ee re Nas evaporated, pour upon the residue » eEnougn aitiutve SsoOLu- , oA , ae t - ee - we ee de om £2 4. fs. tion om 312.1) pAUrLe acia ( pret par Y @aCldad Oo Dad ws Wave CG ) QO 7 4 cover the residual film, ue is permeated) and then carefully decant the Liquid into the bottom of a small wetted filter that is set in a small funnel in the upper neck to a separatory funnel of about 8% capacity and contain 10 c. c. chloroform. Filtration will be rapid, especially if a straight funnel be en , cover the residue in the dish with acid water, warm it as before, and again filter through the same paper > Pee VE ae TE ee ee (, > aT T j afivacing genviLy until the resid- c 4} pouring the Liquid this time, around the inside of the top of the paper. Repeat the operation, stir caine i I (if any remains) in the acid water well, the time, by leans la eflass roa. wUCN J SS4ins , es } 11 Las 0118 as well as chloronhvill 48 pass into the chloroforn + . ,) ~ a? Lukes : 3 : ea et iin 7 , 2 - = , ‘ and are mechanica ba MIixea WLtad tne Wa ver, are £613 L ey ye eee ee jee ae he a ies p a 4 1, en f nA , ‘ wetted filter by this operation, It has been found out ry) Nw a a] te oy 40 Vr gy > Anat fre ‘ ‘ +14 ae | ‘ ! 7 a ‘ | iileal 1 EXD E LMents 5) LIAL IN L1Op lv UCancb C8 ALKALOLGA Le hleal o e 1. 2 - > = “a te | + = 5 te ~ TAT ~~ + ‘ > 72 ye 4. e y ~ e a ’ - ait Extracted ov convact with the first acid watery » ena COM ich yee eee " ‘Tn 9 Ae 7 a a ee LA awa lade ple LEeLy NS ae second; VAs ssh OL GUES! LO a roid ALLY LOUSS 7 & 1.) a ee chy: & 2 ot : : a ae ae ae | Re Po ee yee ae Ee boiarad extraction is advis Ce Usual]. Yr. © ccentin Si 1h . 4 c ay tS ee ee 1 Se a Ra 1 Fe ee ee eee ae, a ee ana very O11} aArugs ) tne undissolved residue i SB Cons iaer > a din ae ets 7 See sa cies CAD es. 4 a: * ee ee OA i ci vAE WOK Sas Neen vorovoer ve v WoEil Wd hon @ & to LILLS DO Lt & UILE - - v - + d alkaloid, practically free from such impurities as can fol- =o Raids oe J . > eee Se he Ya | - a = = ee St avion . Low into the alkaline cholo orin, WiLi now nave neen transe rs = ber As ios oa Ml el) Ohi 4 n terred to the mixed acid AvEMs aos | xT 1. = +1, re | “Po Ce eg om | | =) oO Le Notes on the 4th s LEepse- Ou LCKLY COG the acia 7 2 man 4 i ske A be 2 Tia} 4 os ary eh ‘ va. = J y * + t ‘ Mam ALGUAC ’ MARE LL GALKALLING WLI ammonia ’ Wii. FT OVa Ge u LOUNCGa= er s Bidet hee tee ; Pa ia iist Sis fe ee Te : LE vely » NOL OY SNaKking 9 PUL NY a CAarctiit With three portions of chloroform of 10 vlem separat Lely into a tared dish and heated m = i aa 5 2 7 ~ a7 Y 4 _ LNe@ aisnA here A2ZALN SnNOULG pe Li t S - ea % O ) L residue ney be thin and easily dri 7 i rv ents sthgePationds and for this ohJ ect ; ; J ussayists and sensitive etd 1e amounts of fluid extracts are eferable. Under such \-~ ditions, the residue resticak is reacnes constant weight a: s00n as the chloroform evaporates. When the last portions of the Cc} 110 ror orm LAV € & VYapo rea veQ, GOO. Wile dg ish Ln @&es ie - vor, cover and weigh at once, This alkaloidal residual is obtained froin chloroform, and if that Liquid is enveloped in the resid dum, the 068% Way to bring it to constant weight is to heat it in a drying oven. Even here, chloroform is ex- tremely hard to get rid of and long and h go heat are often necessary to drive off the last traces, In this connec- tion, do not gorget that desiccators, either Lime, sulphu- ric’ acid or calcium chloric @, are dryers of aqueous residues ana that they have no affinities for, and do not abstract chloroform VAaDOrsSe (A great Many assavists prefer to work ia =~ ‘ a) mt oc 7 , thd = tet, ” : Sm ~~ 1+» An 4 4 . Larg GANMOUNGS « SLOWS VC6T 4 t LS eviaent el LE | WLU & * OG LaAti ipulation and accurate balances there is less risk of erro in the manipulation of 5 ec, c. fluid extract. than with amounts Large enough to necessitate previous evanvoration or subsequent trouble and uncertainty in bringing the resid ue tO constant weignt, With such drugs as nux vonica and inchona, possessed of a large anount of stable alkaloids ’ sxists for working large a lounts , especially with cinchona, in which the alkaloid cinchonine is so in- soluble in chloroform and ether, With such as ipecac and aconite, possessed of evanescent alkaloids that are prone to disappear during manipulation, too great care cannot he ob- > , served in shortiz tne orocess ana ave iding ine destructive ‘ ie q « - nN = | ! - > — a 4 : 7 action of heat and chemical manipulation, Some of 1\ESC alkaloids wear ou? rapidly, and under no case, should an as- say be attempted and interru pted. Finish the work at once and without delay). The weight of the residue expresses in grammes and multiplied by 20 gives the practical alll cnloid al per centage of the fluid extract. ow 62. Method of A. B. Lyons:- Pour into a four oz. prescription vial, 10 grammes of the drug in moderately fine powder, Pour in carefully, exactly 100 c.c. of Prollins fluid (12), cork securely and shake vigorously several times at intervals of a minute or two. Place mechanical shaker for four hours, or else shake freque: ina n during that time. At the end of that time, decant into r n y measuring flask, exactly 50 ec.c. of the clear fluid, trans fer to a shallow capsule or evaporating dish and set i warm place (or expose to current of air) until the ether has nearly all evaporated. Then add 5 c.c. of highly di- lute sulphuric acid (1%) and 10 c.c. of fresh ether, Stir to dissolve in the ether, all the oily and waxy matter that may have separated, and to insure combination of all alka- loid with acid, evaporate the ether completely together wit) any alcohol that may remain. 656. Filter the aqueous fluid through a very small filter, into a 1 oz. prescription vial, which should have & square shoulder and a good lip (or else filter at once into a perforator and finish the process by method of Carl Schwickerathy, Treat the residue in the capsule with 3 CeC. Of water slightly acidulated and 5 to 10 ec.c. ether, stir well together, evaporate off the eter, and pass the aqueous fluid through the same filter as first solution into a vial (or else perforator). Test a small drop of this fluid with Mayer's reagent, on a mirror. If it con- tains more than a trace of alkaloid, repeat the washing of the residue once more, with 2 c.c. of water and 5 c.c. of ether. This should not ofen be necessary, but the filter may be washed finally, with a few drops of water. 64, We have now, an aqueous solution, containing all the alkaloids from 5 grammes of the drug. In this, for rough approximate work, we may estimate the alkaloid by the titration with Mayer's reagent, when this is applicable, or by other volumetric processes, as by Wagner's reagent, but in exact work, the alkaloid must be extracted and weighed, or titrated with standard acid and this consumes hardly more time than a direct titration of the acid fluid, 65. The procedure for extracting the alkaloid is as follows:- Pour into a vial containing the acid solution, 15 c.c. of ether, shake well, let separate, pour into a sec- ond similar vial, containing 3 c.c. of slightly acidulated water, Shake together, let separate completely, and pour off the ether into a container for waste ether, (Rarely a second washing of the ether with water may remove traces of alkaloid and it is always best to take this precaution). Repeat the double washings of the contents of No, 1 and No, &, with one or two successive portions of fresh ether (15 CeCe) until all traces of chlorophyll and waxy matter are removed; the ether is to be poured off each time as closely as possible, without loss, 66,. Now add to No. 2, two or three drops of water of ammonia (10%) and 20 c.c, of ether, shake immediately fif- teen seconds and let separate, (Make sure that the ammonia is in excess, by treating the vapor in the vial with red litmus paper, which must not be allowed to touch the neck of the vial. If the paper is not made blue, add more am- monia and repeat the shaking). Pour off the ether into No. 1, add water of ammonia in excess, perhaps 10 drops, and immediately shake vigorously 30 seconds. Let separate, return the ether to No. 2, but shake this only once and then let stand several minutes, so that tne ether will sep- arate completely from the watery fluid. Now add to No, i, 15 c.c. of fresh ether, shake well together and let separate, The ether is now to be decanted carefully from No. 2 into a tared beaker, to be replaced by that from No. l. 67. A third portion of ether, passed in succession through No. 1 and No. 2, will generally extract all the al- kaloid if it is one freely soluble in ether (If not, it is better to use a mixture of 15 cec. ether, and 5 c.c,. cnlor- oform for the first washing to be followed generally with pure ether for the subsequent washings). In any case, test the residual aqueous solution in No. 1, which should be generally quite clear, by placing a drop of it on a mirror, adding acid in excess and then a drop of Maver's reagent. There should not be produced, more than a faint cloud, al- though traces of alkaloid will often be found even after five or six washings. 68. Evaporate the ethereal solution on the water bath to constant weight. If chloroform has been used in the ex- raction, redissolve the residue once or twice in alcohol and evaporate to expel persistently adnering traces of chloroform, Weigh the residue, The weight of the alkaloid in decigrammes multiplied by two, or the weight in centi- grammes divided by five, will be the percentage of total alkaloids contained in the drug. 69. After weighing the crude alkaloid, dissolve it ii 5 ¢.C. alcohol, add 5 c.c. of No. 1-25 hydrochioric acid and 25 c.c, distilled water. Be sure that the alcohol and water contain no traces of acid or of alkali; add & drops of Brazil wood indicator (or haematoxvlin or cochineal) and titrate backwith No. 1-25 alkali. The amount of alkali consumed must be subtracted from 5 c.c. to give the acid equivalent of the alkali present. In case of alkaloids having only feeble alkalinity, the alkalimetric test is, of course, superflous. 70. For rapid work, in the case of alkaloids that ad- mit of determination by alkalimetry, the assay may be abbre= viated by evaporating the original etynereal extract (50 c.c,) to dryness, taking up with 10 c.c. acid free ether, evap- orating once more, adding 10 c.c. of acid free ether, togeth- er with 5 c.c. of No. 1-25 acid, evaporating off the ether and titrating back with N 1-25 alkali, as described in the last paragraph. The alkaloid can be afterwards recovered from the solution in the usual way if this is desired. 71. Short assay process #2- Dr. Iyons:- Put intoa 4 oz prescription vial, 12 grammes (this quantity is suit- able in the case of drugs containing less than 0.8 percent, of alkaloid. If there be as much as 1 percent., 10 grammes of drugs is sufficient, if five percent., not more than 4 grammes of drug should be used) of the drug in fine powder. Pour in exactly 100 c.c. of a mixture of ether eight vol- umes and chloroform one volume, cork securely and shake well. After 10 minutes, shake once more, add 5 c.c. water of ammonia (10%), cork and immediately shake vigorously, repeating this several times at an interval of a minute or two. Place in the mechanical shaker four hours, or else shake at frequent intervals (once in five or ten minutes) during that period, then,if the drug does not settle promptly leaving a clear supernatent liquid, add water suf- ficient to cause it to aggregate into lumps on shaking (from 15 to 25 c.c. generally suffice). In any case, de- cant exactly 50 c.ce of the clear ethereal fluid into a measuring flask, and thereafter follow the instructions given under Assay Process, No. l. (62 et seq.) 72. Instead of evaporating the ethereal fluid, it is practicable to wash out from it, the alkaloid, in the fol- lowing manner; transfer the fluid to a separator, add about 21/2 e.c. of dilute hydrochloric acid (10%) and shake to- gether. Wake sure that the acid is in excess, best by adding a drop of some indicator, add more acid if necessary, and water enough to make up 5 c.c. in all of aqueous fluid. Shake together 30 to 60 seconds and let separate. Draw off the acid fluid into a one ounce prescription vial, treat the ethereal fluid with four or five successive portions (3 c.c.) of sligitly acidulated water until all the alka- loid is removed, Test a small drop each time after the sec- ond washing, on a mirror, with Mayer's reagent. Add the first portion of the contents of the vial (No.1), put the next two or three washings into a second vial (No.2) and the last into a third vial. 75- To recover the alkaloid, add first to No. 3, a drop of water of ammonia and 5 esc. of chloroform mixed with 15 c.c. of ether; shake, let separate and decant the ethereal fluid into No. 2; add 2 or 3 drops (excess) of water of ammonia, shake, let separate and decant into No. 1; add excess of water of ammonia (perhaps ten drops, but make sure that the ammonia is in excess by testing the vapor in the bottle with red litmus paper), shake together well for 50 seconds or more, let separate and decant into No. 3, which now contains little but water; shake together once, let stand fully two minutes for complete separation and de- cant into a tared beaker, Put into No» 2, 20 c.c. ether, which is to be passed in succession through No. 1 and No. 5, in the same manner as before, and follow this with one or two additional portions of ether, 15 c.c. each until as- sured that the whole of the alkaloid is removed, 74, Finally evaporate the solvent at a water bath heat and dry to constant weight, as in process No, (68) and (69) (The details of the. process have been given quite minutely for the benefit of beginners). The object of the final washing in vial No. 3 is to avoid the possibility of carry- ing over with the alkaloid any of the aqueous mixture of vial No. 1, which is heavily charged with a salt of ammonia. 75. Short assay process No, 3- Lyonst- This differs from Process No. 2 only in using, for extracting of the drug, light petroleum (petrolewm benZin) instead of a mixture of chloroform and ether, A benzin, having a boiling point of 80 degrees C. is generally suitable and even to be preferred to that having a lower boiling point. In particular assays it will be found advantageous no doubt, to use even a less volatile hydrocarbon oil, but this has not yet been experi- mented upon fully. It will be found best, generally, where petroleum benzin is used, to follow the procedure of (172) unless emulsification occurs, and in this, his experience is not common, 76. Short Assay Process No, 4- Lyons:- Proceed ex- actly as in process No, 2, but use, for extraction of the drug, a mixture of chloroform one volume, and ether four volumes, 77. Some modifications of the above processes suggest themselves, as likely to be of service, although not yet fully tested in practice. These involve the use in the first stage of the process, of some agent to fix organic acids and other compounds which go into solution in ether and chloroform, Ferric Chloride or lead acetate suggest themselves; possibly litharge might answer the purvose, The first may be used in the following way. Treat the drug in the beginning, with an ethereal mixture, 100 c.ce, con- taining 0.2 to 0.5 gramme of ferric chloride, agitate fre- quently or continually during one hour, then add excess of water of ammonia and continue the process in the regular way, Or, the drug may be moistened in the beginning with an aqueous solution of lead acetate or of ferric chloride and, after an hour, treated with ether (ether, chloroform or other solvent) and ammonia in excess in the usual way. 78, Method of Lyman F. Kebler (11), A modification of that of Keller. Place 10 grammes of the powdered drug ina 250 CeCe flask, add 25 grammes chloroform and 75 grammes of ether, cork the flask securely, agitate the flask for sev- eral minutes, add ten grammes of water of armonia (10%), and agitate frequently during one hour, On adding 5 grammes more of water of ammonia, the suspended power agglutinates into a lump, the liquid becomes clear after standing a few minutes, and can be poured off almost completely; 50 grammes of the clear fluid are taken for the assay and treated by one of the following methods. 79, Process 1li- Place the ethereal fluid in a beaker, evaporate on the water bath, add 10 c.c,. ether and evap- orate once more. Dissolve the residue in 15 e.c. alcohol, add water to slight permanent turbidity, haematoxylin, Bra- Zil wood or cochineal as indicator, and a measured quantity of volumetric acid; titrate back with centinormal alkali. 80. Process 2:- Transfer the ethereal fluid to a sep - arator, treat at once with 20 c.c. of acidulated water, after thorough agitation and complete separation, remove the aqueous solution to a second separator, Repeat the above Operation twice with 15 c.c. of acidulated water and add to first washing. Wash out the alkaloid from the aqueous liq- uid, after adding ammonia in excess, with three portions of a mixture of chloroform three volumes, ether one volume. The ether-chloroform is then evaporated off in a tared beaker, the residue twice dissolved in 8 c.c. ether to carry off the last traces of chloroform, dried on water bath to constant weight and accurately weighed, It may then still be dissolved in alcohol and titrated with standard acid and alkali, The first procedure yields naturally a somewhat higher figure. 81. Method of Prescott and Gordin (12):- One to four grammes of the finely powdered drug is weighed into a low, wide-mouthed vessel with a round bottom, holding 8 or 10 ounces and having a well fitted cork, such as a screw top ointment jar (an ordinary tea-cup fitted with a specie cork answers well.) The powder is rubbed up with a small pestle to a fine paste, by adding a little of a solvent mixture, composed of stronger water of ammonia and alcohol, each 9 ¢.c., chloroform 10 c.c., and ether 20 c.c. Then a few more cubic centimeters of this mixture are added, so as to have the drug well covered with the liquid, using in all, about five times the amount of the drug taken. The vessel is corked with the pestle inside and is set away for about four or five hours, taking care to agitate by circular movement, very frequently, during that interval. After that time, the cover is removed and the vessel kept ina current of air, stirring frequently until all odor of an- monia has disappeared. With a good draught and frequent stirrings the powder will be almost perfectly dry in about two hours. The vessel is then put in a vacuum desiccator over sulphuric acid for about four or five hours, 82. An amount of powdered sodium chloride, equal to about five or six times the amount of drug employed, is then carefully mixed in, with use of the pestle and the whole thrown into a small percolator, one provided with a glass stop cork and having a plug of cotton at the bottom, The vessel is then cleaned out several times with small Quantities of sodium chloride and the cleanings added to the percolator. The mixture in the percolator is then covered with a piece of cotton which is pressed down with &@ piece of glass and a suitable menstruum, usually chiloro- form, is poured slowly into the percolator until the men- struum reaches the stopcork, The latter is then closed, the percolator covered and set away for five or six hours. After that time, the stop-cork is opened and the drug ex- hausted with the menstruum, until 10 drops of the percolate evaporated on the water bath on a watch crystal, and the residue taken up in a few drops of acidulated water; the solution shows no turbidity whatever on adding a few drops of Wagner's reagent, When finished, the percolate, which is received in a flat evaporating dish, is placed in a good draught, at a temperature of about 30 degrees C. When the liquid is reduced to a very small volume, ten c.c. acidu- lated water, ( if an alkalimetric assay is intended, the acidulated water in the operation should be standardized and taken in definite quantities), are added, and then a few cubic centimeters of ether or petroleum ether, so as to have an ethereal liquid cover the aqueous solution, (if the menstruum is all evaporated off, it will be sometimes dif- ficult to dissolve out the alkaloids with acidulat:-d water. If chloroform be used, coming below the aqueous layer, it evaporates too slowly), when the whole is stirred witha glass rod until all the ethereal liquid is driven off, The liquid is then filtered and the evaporating dish and filter washed several times with acidulated water, In this way, is obtained a colorless solution of the alkaloid, which can be worked up for any method of assay. 85. The iodometric Method:- In the periodide method of assay, the final alkaloidal solution obtained, whether by methods (81) and (82), by Dr. Lyon's methods, or by any other method, this final solution representing a definite quantity of the drug to be assayed, is poured slowly, and with constant stirring, into a flask holding 100 c.c. in which has been previously added 20 or 30 c.c. of a stand- ardized solution of iodine and 1 or 2 e.c. of dilute hydro- chloric acid (U.S.P.);(except in case of morphine, an ex- cess of acid is not hurtful and even promotes the separa- tion of the periodide, Hydrochloric acid is to be preferred 4 to sulphuric acid). The flask is then filled up with dis- tilled water to 100 c.c., stoppered, and well shaken until the periodide has separated out. The supernatent liquid to be perfectly transparent but of a red iodine color, Fifty c.c. are then filtered off and in this portion, the excess of iodine determined by titration with standard so dium thiosulphate. The amount of iodine consumed, multiplied by a suitable factor, gives the amount of alkaloid present in the quantity of drug taken, 84, In the case of several alkaloids being present in the drug, a mean iodometric factor can be- deducted in the same way as is done in alkalimetric assay. It is to be noticed that, should there be no precipitate with iodine, but only a slight turbidity, then the drug is extremely poor and a much larger amount must be taken for the assay. On the other hand, should the Supernatent liquid, after adding the alkaloidal solution to tye iodopotassium iodide solution and separating the periodide by shaking, have very little color or be almost colorless, then it is certain that the drug is very rich, and either a smaller quantity of the drug or a larger quantity of the iodine solution must be employed in the assay, 85. All assays should be made in duplicate. The careful operator will always provide for verification of his results, by some form of duplicate assay. In most cases,.it is not necessary to make two, wholly independent assays, although that is the most satisfactory procedure, In the assay of a crude drug, we more often make a single weighing of the drug, which is exhausted by some appropri- ate solvent and the solution made up to a definite volume. Of this, we then take for assay, two aliquot parts, follow- ing preferably different methods of treatment. A method of assay which in itself gives only approximate results, as for example a titration with Mayer's reagent, furnishes valuable confirmation of results reached by more scientific and exact methods and such a duplicate may be all that the operator has the time to carry out. 864 Estimation of Alkaloids by Alkalimetry, The alkaloidal residues obtained by extraction with immiscible solvents and commonly weighed as total alkaloids, are never quite free from foreign substances, With reasonable care in manipulation, they are generally so nearly pure that we shall make no serious error in accepting their weight as practically that of ithe alkaloid itself, and when the a- mount of alkaloid is large, as in cinchona bark, the gravi- metric estimation is close enough for the professional chemist. When the quantity of alkaloid, however, is very small, the error is often considerable; impurities may constitute from ten to fifty percent. of the alkaloidal residue, We must therefore, have some check upon the re- Bults obtained by weighing, and this, in the majority of cases, is supplied in the alkaline reaction of the uncom- bined alkaloids, The most of them can he determined with great exactness, by titrating with standard acid, 87, Unfortunately, in drug assays, the residue gener- ally contains two or more alkaloids, having different equiv- alent values, so that even alkalimetry does not give us the definite, exact result we desire, It enables us, however, to check our gravimetrie result and, in most cases, the -- 6 limit of error is not greater than five percent of the en- tire amount, as against a possible thirty or even fifty percent, of the entire amount in the gravimetric method. It must not be understood that errors as large as this, are common where gravimetric methods are followed; it is suf- ficient that even with reasonably careful work, they are possible, and hence the operator should always control his work, when practicable, by alkalimetry., The beginner must remember, however, that in experienced hands, the alkali- metric process admits large possibilities of error. 88. Direct titration with standard acid:- Dissolve the alkaloid in ether, chloroform, or other immiscible sol- vent (10 c.c.), put the solution into a stoppered vial of Clear glass, add water (5 c.c.) colored with methyl orange (A. H. Allen) or other suitable indicator, Add the stand- ard acid (N-25, hydrochloric acid) little by Little, at last, a drop at a time, s”aking after each addition. The end reaction is sharply marked by change of color in the aqueous fluid, 89. Residual titration with Iodeosin as indicator:- Dissolve the alkaloidal residue in a little acid free ether containing iodeosin (2 milligrammes to litre) add an accu- rately measured quantity of standard acid N-25, in excess of what is required to neutralize, transfer to a stoppered vial or flask of clear glass, and titrate with alkali N-25, shaking the container well, after each addition. As soon as the alkali is in excess, the iodeosin is taken up in the aqueous solution, imparting a red color to it. The indi- cator is not suitable for titration of quinine, but answers well for most of the alkaloids. 90, The ordinary procedure:- (1) Dissolve the alka- loidal residue in 10 ec.c, of acid free ether, add water 10 C.C., and a drop of indicator, preferably, Rrazil wood, cochineal or haematoxylin; add from a burette hydrochloric acid N-25, until after stirring well, it is in decided ex- cess. Allow the ether to evaporate, It should leave scarcely any residue, If there is any appreciable residue, pour the acid solution into a clean beaker, treat the resi- due with 5 c.c, fresh ether and 1 c.c. of acid N-25, evap- Orate off the ether and add the acid contents to the solu- tion in the second beaker, Now, titrate back with N-25 al- kali until the color of the solution changes permanently, that is, so that the original color does not return within 20 or 30 seconds, ‘Subtract the quantity of alkali used from the total acid taken, and calculate the quantity of alka- loid by the tables following in (93). Note that the rela- tive strength of acid and alkali must be fixed under condi- tions similar to those of actual titration and with use of the same indicator, 91. Alternative Method (2):- Dissolve the alkaloidal residue completely in 5 c.c. acid free alcohol, add 10 c.c. N-25 hydrochloric acid or such a quantity as shall be more than sufficient to neutralize all the alkaloid, (The weight of the alkaloidal residue, already determined, wil! indicate the quantity required); Add 40 e.c. water, tw drops of indicator, and titrate back with N-25 alkali. It is important that the solution contain not more than one fifth its volume of alcohol, as a larger proportion will interfere with the sensativeness of the indicator, partic- id ularly haematoxylin. One plan is to add excess of standard sulphuric acid and evaporate off most of the alcohol before titrating. There is, however, possibility of loss of some delicate alkaloids, from the action of an excess of sulphu- ric acid, during the evaporation, 92. Make sure in all cases, when an alkaloidal solu- tion is evaporated to dryness previous to titration, that there is no possibility that it be reached by acid vapors, also, that the heat to which it is subjected be not suffi- cient to cause chemical changes in the alkaloid, It is ad- visable, indeed, of the more unstable alkaloids, to avoid any application of heat exceeding about 45 degrees C. It is impossible that in driving off chloroform the solvent itself may become decomposed, furnishing acid to vitiate the result, In any case, if the titration gives results much lower than the weighing, we should suspect some sourc- és of error affecting the former rather than the latter, and a duplicate experiment should be made, avoiding, as far as possible, the above mentioned dangers. 93. Determination of Alkaloids in 3alts by Alkélimet- ry. While to most indicators, alkaloids are alkaline in lein. Consequently, when a solution containing an alka- loidal salt is titrated with standard alkali, in presence of this indicator, the whole of the acid appears by the ti- tration, as free acid. If a solution containing an alka- loidal salt together with excess of acid, is divided into two equal portions, and these are titrated with standard alkali, using in one case, Brazil wood, haematoxylin or cochineal, and in the other, phenolphthalein, we shall get different results, the difference representing the quantity of alkaloid present in one half the solution. We may thus determine the amount of alkaloid even though it has been partially neutralized through accident or carelessness. The method is not applicable in the case of atropine, nar- cotine, coniine, colchicine, caffeine and some other alka- loids. It is important that the standard alkali used for the titration be free from carbonate, 94, Normal equivalents of the more important alkaloids, The following table is useful in interpreting the results of titration, Table on the next page. A A A A A A A A A A A A A A A Aconitine---------- -647 25.9 1.294 0.518 0.431 0.259 Atropine------------289 11.6 0.578 0.231 0.193 0.116 Berber ine-----------335 13.4 0.670 0.268 0.223 0.134 Bruc ine-----~-------393 15.7 0.786 0.314 0,262 0,157 Cinchonine------~----293 11.7 0.586 0.234 0.195 0.117 Cinchona Alkaloids--314 12.6 0.628 0.251 0.209 0.126 Cocaine--------- ----3505 12.1 0.606 0.242 0,202 0,121 Coniine-------------127 Sel 04254 0.102 0.085 0.051 Emet ine-------- ----- 254 10.2 0.508 0.203 0,169 0,102 Gelsemine----~--~----408 16.3 0.816 0.326 0.272 0.163 Hydrastine-----~~---397 15.9 0.794 0.318 0.265 0,159 Morphine----------- ~284 11.4 0,568 0.228 0.190 0.114 Nux Vomica Alkaloids363 14.5 0.726 0.290 0.242 0.145 Physostigmine-------275 11,0 0.550 0.220 0.183 0.110 Pelocarpine---------208 8.65 06416 0.166 0.139 0.083 Quinine-------------323 12.9 0.646 0.258 0.215 0.129 Strychnine-~~--------233 13,3 06666 0.266 0.222 0.133 Veratrum Alkaloids--687 27,5 1,374 6.550 0,458 0,275 i ee ee LS A A A A A A A A A A ea ce Also aconite root and leaves, but results are without value Also belladonna root and leaves; Hyoscyamus and stramonium leaves and seed, Also ipecac Also yellow jesamine Only feebly alkaline; with ordinary indicators, titration not satisfactory. Also jaborandi 95, Kjeldahl's LIodometric Method for alkaloidss- Another plan for the exact determination of alkaloids, based upon their power of neutralizing acids, has been proposed by Christensen (18). It is a modification of Kjeldahl’s iodometric method of estimating free ammonia. The alkaloid or alkaloidal residue is dissolved in an excess of sulphuric acid, N-25, an excess of neutral so- lution of potassium iodide (1-15) and of one of potass- ium iodate (1:25) is then added, whereupon iodine is liberated in quantity exactly proportional to the free acid remaining. If the solution is then titrated witha solution of sodium thiosulphate N-25, then the quanti- ty of this solution deducted from the quantity of stan- dard acid taken, the remainder will be the quantity of acid N-25, consumed in neutralizing the alkali. It is a pretty method but seems to have no advantage over the simple alkalimetris process. 96, Volumetric Estimation as Chlorides- Another procedure may be adopted for determination of alkaloids which form strong combinations with acids, and which are not too easily decomposed by excess of acid. The alkaloid in the ethereal solution may be super-saturato: with an ethereal solution of hydrochloric acid, -vapor- ated by a gentle heat, the residue taken up with alcohol once or twice, and dried again to drive off complete- ly excess of acid, and the residue dissolved in distil- led water and tritrated with silver nitrate standard solution N-100 to determine the chlorine and thus indi- rectly the quantity of alkaloid present. 97. The method of Gordin and Prescott (14)3- Messrs. Gordin and Prescott observe that while from a theoretical point of view, one of the best methods of estimating the alkaloids is undoubtedly the alkalimetric estimation of their basicity, the weakness of their bas- icity is often so great as to cause acids combined with them to react upon most indicators and particularly phe- nolphthalein, as if the acids were free. The end re- action, unlike that with sulphuric or hydrochloric acids and standard alkali, is therefore indefinite and of lit- tle practical value. A Simple improvement of the methog however, makes it possible to estimate all alkaloids capable of forming salts with as much sharpness as is obtained in inorganis alkalimetric analysis, and admits of the use of phenolphthalein as indicator in all cases where carbonates, etc. are absent. This consists in taking up the alkaloid in an excess of standardized nin- eral acids then precipitating the alkaloid witha slight excess of some delicate reagent like Mayer's or Wagner's making up the mixture to a definite volume and filtering off one half of this after the precipitate has formed completely. In this filtrate, the excess can then be accurately determined by the use of standard alkali and phenolphthalein as indicator. In case Wagner's reagent is used, the filtrate mst first be decolorized with sodium thiosulphate, Whatever the composition of the precipitate may be as regard to mercury and iodine, the alkaloid always falls as a salt and therefore takes up an amount of acid which is equivalent to the combining weight. Hence, on deducting the excess of acid as de- termined alkalinetrically from the total quantity of acid employed, the amount combined with the alkaloid is at once ascertained and from this, the amount of alkal- oid is readily calculated. In order to obtain the best results, the acid and alkali should be standardized for each alkaloid, by a weighed quantity of that alkaloid, and proceeding as above described. 98. Acidimetric Titration with Ammoniacal Cupric Oxide (15); EH. Palieres has employed an ammoniacal so- lution of cupric oxide, with advantage, for the acidime- tric titration of alkaloids. The method is bases upon the fact that as soon as the last trace of uncombined acid is saturated, a distinct turbidity is produced in a solution of the alkaloid, prepared by dissolving 0. 10 Gm. in 20 c.c. n sulphuric acid. The reagent is pre- pared by dissolving 10 Gm. of cupric sulphate in about 500 c.cs of water, adding ammonia until the initial pre- cipitate is redissolved, and then enough distilled water to make 1000 ¢.c. The test is made in a glass vesse!] Placed against a black background, the standard copper Solution being then run in until a permanent turbidity results. In the case of cinchona, the total alkaloid may be determined in the first extraction, since the ac- companying impurities do not affect the appearance of the cupric oxide precipitate. 99. Gravimetric Estimation of Individual Alkaloids $3 For exact gravimetric determination of individual alkal- oids, the precipitates produced by gold and platinum chlorides are well adapted. When these precipitates are ignited, the residue consists of metallic gold or Platinum as the case may be. In general, the procedure is like that for determining potassa as a platinum con- pound. The alkaloid solution is evaporated with a Slight excess of hydrochloric acid and an excess of the reagent nearly to dryness; the erystalline precipitate is washed with a little water or with delute spirit, care being taken to remove all excess of reagent and all mineral salts, the residue ignited and weighed, best in &@ Gooch crucible. 100. The following table gives (a) the weight of the respective residue of gold or platinum correspond- ing with one hundred parts of the pure precipitate(16) ; (b) the factor of which to reduce from the weight of the residue, the alkaloid it represents(For example, a res- Pa idue of 27 Milligrarmes of gold in an atropine estima- tion would correspond with a precipitate of the double chloride of gold and atropine weighing 27x100 divided by 81.37 milligrammes or with pure atropine weighing 27x1.46- 45.4 milligranmes. Table of gold and platinum equivalents found on the next page. Table. a ncn a cr a a an eee Atropine-----------------31,37 1.46 “--- at Berber ine--------~-------29,.16 1.70 18,11 5045 Brucine------- wate eee en ---- ---- 16.52 4,05 Caffeine--- --------------37,02 0.98 24,58 1.99 Cinchonine--------------- ---- ---- 217,356 1.50 Cocaine---------~--------50.68 1,54 ----- ---- Code ine= ------------<---- ---- ---- 19,11 5-06 Coniine--------~----+--~----+ <---- ---- 29.38 1.30 Emet ine--~--+-----+-~---++- ---- -~--- 29.70 1.30 Gelsemine(Gerrard)-------36,90 1.04 16.70 2209 Gelsemine(Thompson)------29,.80 1.63 18,58 we 00 Hy oscyamine--------------354,60 ---- ----- ---- a ia a 19.51 2692 Bisetinede «<<< --=-<<20-2<< «--- — 34.25 0.62 Pelocarpine-------- +4400 35.50 1.06 23.6 2.13 Piperine----+--------s-<<- <---- ---- 12.70 5,85 Quinine-------------<- ‘ . . a> oO * oS © 2) . Oo nw wo > ~ av) ep =) oo Strychnine----~------+---=29,15 1.69 18,16 3642 i ‘ i i i i Theobromine-- we Hees aoe ---- 25605D Le 8D Veratr ine--------~--+------21,01 3e0L 289+ == -- ---- yo 101. Volumetric Hstimation of Alkaloids by Mayer's Reagents- Most alkaloids are very completely precipi- tated from acid aqueous solutions, by the solution of potassio-mercuric iodide, known as Mayer's Reagent. The precipitates are more or less soluble in alcohol, ether, acetic acid, solutions of iodides and so in an excess of the reagent. In alkaline solutions, ammonia also is precipitated. The fluid therefors is to be tested for alkaloids by this reagent, must be slightly acid in reaction, and must be nearly free from alcohol and other fluids similar in their solvent action to al- cohol. The presence in the solution, of certain salts, notably of iodides, has a marked influence upon the final result. 102. If Mayer's reagent is added little by little to an acid solution of an alkaloid, the first portions will produce a heavy precipitate, but soon a point will be reached where a drop of the reagent only produces a faint cloud in the solution. It may be still necessary to add a considerable quantity, ten or twenty drops, of the reasent béfore the point is reached, when a furthor addition produces no effect, and it will then be found, in the case of most alkaloids, that a large excess of the reagent has been added, so that addition of fresh alkaloidal solution causes a heavy precipitate. The er- cess will constitute a certain proportion of the fluid at the end of the titrations hence, the most dilute the solution titrated, the larger the quantity of reagent required to complete the precipitation. 1038. We cannot, therefore, fix for each alkaloid, a definite invariable titration equivalent. We find, moreover, that the degree of acidity of the alkaloidal solution, the manner of adding the reagent, any varia- tion, in short, in the mode of procedure is liable to influence the result materially, so that quantitative determinations of an alkaloid by titration with Mayer's reagent are of value only when carried out under cer- tain laid down conditions. We find, further, that at best, there is a provoking variability in the composi- tion of the precipitates, so that even when we collect and weigh these, we obtain only approximate results. 104-6 In spite of these drawbacks, a good many al- kaloids can be determined with reasonable exactness, by titrating with Mayer’s reagents and no doubt, in the hands of an experienced person, the method will be undex taken with more confidence and will actually give better results than alkalimetry. For certain alkaloids, it is true, it is worthless, for sone others, too troublesome to be recommended; the same may be said of the alkal- imetric method; in either case, we arc to prove all methods and hold fast to that which is good, “yy Mayer's reagent is very good in rough valuations ol! ipecac and of colchicun, and in the determinations of strychnine ani berberine. Besides this, it is useful in determining rapidly, whether or not a given tincture or fluid extract is deficient in aikaloid. 105. Method of Titrationwith Mayer's Reasent. Put the solution (10 or 20 c.ce) to be titrated, which should contain as nearly as possible, 0.5 per cent. of alkaloid, into a small cylindrical measuring glass, or a roughly graduated test tube and note its volume. Run into it from a burette, Mayer's reagent, N-20, 15 drops, or, if you havean idea of the quantity of reagent you are likely to require, use one half of that quantity. Filter into second test tube, selecting a filter which will hold the whole of the fluid at the end of the titration, but not much more. 106+ When the fluid has nearly all rin through, set the funnel in test tube No.1 and add to the filtrate two drops of “ayer’s reagent from the burette; if this produces a dense precipitate, as it should, add 10 or even 15 drops of the reagent, return to the filter, us- ing the fluid that has filtered meanwhile, into No.1 to rinse No.2, returning all to the filter. Proceed in this way until the precipitate begins-to be scanty, when the quantity of reagent added at once must be re- duced accordingly, until finally it becomes a single drop. As the end of the precipitation is neared, allow nearly the whole of the liquid to pass through the fil- ter before adding more r«agent, and filter twice if ne- cessary, to secure a perfectly clear fluid. 107. The reaction is taken to be complete, when the aldition of a single drop, or at most, two, of re- agent does not produce at once a turbidity in the fluid. It will often happen that one or two drops will produce a faint cloud, which dissapears as it mixes with the rest of the fluide If a larger quantity of reagent be added, 2 permanent turbidity, or even a precipitate, is produced, but this should be ipnore4. Uniformity of practice in fixing the end point of the reaction is, of course, indispensible. The operator should practice with solutions containing a known quantity of alkaloid, and so determine its equivalent as modified by his per- sonal equation. If, at the close of a titration, it appears that the original solution was stronger or weak- er than that recommended above (0.2 to 0.5%), a new solution should be made, and of a strength approximately of 0.5 per cent. and the titration repeated with this solution, 108. Hereth's Method (17), of titrating with Mayer's reagent consuners rather less time than that given. above, and is carried out as followss:. Knowing strenoth of the solution approx imat ely. the alraloidal dozen or more test tubes to be examined, provide half a or vials, into each of which measure 10 c.c. of the solution, To the first, add a quantity of Mayer's re- agent which is believed to be a little less than enough for the precipitation ( make sure that such is the case, before proceeding further, by filtering and testing the solution with more of the reagent). To the second portion, add a quantity of reagent 5% greater; to the Srd, a quantity 10% greater and so on. Let the tubes stand sight hours, then test a portion of the clear su- pernatent liquid from each, by a drop of the reagent. Amongst them, there will be some that will react strong- ly, others that do not react at all. ‘the first one that fails to react, obiously, has received of the reagent, a little more than enough, and the amount of additional precipitate in the one preceding it in the series, will enable us to fix quite accurately the point at which precipitation would have ceased, had the titration been carried on in the usual manner. 109. If this method is to be adopted, it will be necessary, of course, to fix the value of the equivalent for each alkaloid empirically, by experiments carried out in the same mannery which would differ more or less, from those based on the ordinary procedure. 110. Gravimetric Determination by Mayer's Reagent+ Results somewhat more exact and uniform nay be obtained in the use of Mayer's reagent, if we collect and weigh the precipitate instead of depending upon the quantity of reagent consumed. The error would rarely be over 5 per cent. of the total weight, not an ideal exactitude of result, it is trues and yet close enough to sive use- ful information. The reagent mast be added in slight excess, and time given for complete reaction and sepa- ration of the precipitates; in the ordinary routine, say two hours. The precipitate is to be then collected upon a pair of mutually c mnterpoised filters, washed with the smallest practicable quantity of water, applied so as to wash the filters especially. When the filters have drained, press first between folds of filter paper, to remove most of the water, then dry at 100 degrees C. to a constant weight and weigh, or, after the precipi- tate is washed and drained, it may be dissolved in strong alcohol, evaporated in a tared vessel and weighed. 111. Titration of Tinctures, ete., with Mayer's reagent:- It is sometimes recommended to titrate di- rectly with Mayer's reagent solutions prepared from tinctures or fluid extracts, by acidulating, evaporating off the spirit and diluting, if necessary, with water. Such a procedure may enable us to detect any notable deficiency of active principles, but is liable to be misleading, since other substances besids alkaloids are precipitated by Mayer's reagent. Solutions prepared with strong alcohol or with etheral solvents are less likely to contain such substances (albuminoids) but in general \ titration with Mayer's reagent should be practiced only on solutions so prepared that they can contain little besides alkaloidal salts. 112% It must be admitted, however, that direct ti- tration, applied to galenical preparations, does not correctly indicate in most cases, their relative medic- inal strenght, and a titration and standardixation at alle 118. Where several alkaloids are present in the drug, as is aften the case, the titration method, whether with Mayer’s reagent or with standard acid, can only be limited application, wuniéss proceded by a seép- aration of the alkaloids. It may, however, sometimes serve, when the total alkaloid has been determined, to indicate the relative proportion of the constituents, if there are but two, as in nux vomica, and after all a standard bases upon total alkaloid may be as rationally fixed by titration as by weighing. 114. Precipitation equivalents of Mayer"s reagents Only by experimental method can the correct precipita- tion equivalents of the several alkaloids be determined for practical purposes. If solutions are always made so as to contain very nearly 0.5 per cent. of the alkaloid and the titration is made in solutions always containing the same proportion of free acid, there should be with most alkaloids, but little variation in the titration equivalent and it is with these conditions in view that the accompanying table has been tabulated by Prof. Lyons and the column of "Practical Equivalents” should be used where the titration is conducted in the manner described above (105) and what follows. Dragendorff's figures are also given based upon titrations conducted in a some- what different manner. 115. When the solution contains much less than 0.% of alkaloids, closer figures will be obtained by using the "Corrected Equivalents" of the table after having deducted from the quantity of Mayer's reagent used, a correction which consists ofa certain per cente of the whole volume of fluid at the end of the titration. Thus, a titration of cocaine,ysuppose the volume before titra- ting to be 12 Cetey and that 5.25 c.ce of Meyer's re- agent 1-20 have been required for complete precipitation, Then, at the end of the titration, the volume of fluid was 12= 5.25- 17.25 cece. The correction by the table is 8% of this or 1.38 c.c. Subtract this from 5.25 and we have 3.87 ¢ecs as our correctscd figure for quantity or the table after having deducted from the quantity of — = ayer's reagent J ‘h consists : : Gain per cent o le W : ) lid the end of the titration. Thus a titrati) volume before titrating 1 e. J ative Chat 5.2: PT es, Mayer's reagent 1-20 have been required for com} te -ecip- Siataion. Then, at the e the titration, the volume o fluid was 12 plus 5.25 equal 17.25 c.c. The cor tio Sie bepte is 184 eof this or 1.38 'c.c. th 106 this from 5.25 and we have 3.87 c.c. as our corrected figure for quan- tity of Mayer's 2 YZ sonsumed. This l to the corrected equivalent of the table (.0098), indicates the presence of .038 Grms. cocaine LUT LO? instead of NAA KNEG ae q _ . — . - 7 = S ~U4Z400, tne il ire Je SNOULG NAve ; L x MY Ral R GV column of actical Equivalents. a-6.° A seco. itration should be made, if time -and material permit. with a solut; son ce ted go that & cac 5 ee ee oe ee —— c . +, Os on nt contain as much alkaloid as t: 12 Ge used ji > ne irst 2 e : - ; 4 7 ~ ——— = aa ang =. oe ae ~ = hee titration. nithis ere a question of concentra tion by evaporation LU IGLUt bon ; PC wowld be T ~ - » d ~~ “ } — - 4 . 4 - . 4 — A. panes Etter CO AaANDLAE DHNj NE L ; € Cner tinal 4 2 a 5 oa 4. expose the alkaloid of destroying it ,- a principle to be porne in mind in GLC n woich we a Ga ham’ aa) . 7 7 Te - the aliralniad Cne ..¢ a1 WY } mf ALLS L L # we J | AL I om et a he 2 ete) ] > table, based uvon experi- mental data, is to facili : , tions wnere the alkalol is to be determined by tne wei 1 precipitate pro- duced by Ma eagent. [ eisht by the mean value of tie f » find approximately the weight of the aikaloid containe l pal Atate,. Tin 2 precipi- tate fro a ruGine so. < ‘ fliliores es: the factor is stated to be 0.46 > 0.500 The of these is tf) ARQOF Mm 3 pant 2é 04526-0,555 Atropine----- Unsatis- 0.00625 0.0077 5% 0.0088 0.488-0, 461 factory Berberine---- Good 0.02063 0.0263 ----- ------ 0.500-0.520 Brucine-~----- Fair 0.00985 0,0125 3% 0.0139 0.465-0.50% Chelidonine-- -------- SEE ....2 +> -« Rath tid RAE coe e429 Cinchonidine=- Unsatis- ------- 0,0070 ----- ------ 0,.266-0, 303 factory . Cinchonine--- Fair o~----- 00,0071 ----- ------ 0.290-0. 309 Cinechonine--- Unsatis- ------- 0,90090 ----- ------ wee eee =~ factory Cocaine------ Fair cnase—ee M076 8% 0.0098 0.406 Colechicine--- Fair 0.91580 0.0109 8 1-2 0,0149 0.625 Coniine------ Unsatis-=- 0.90625 ------ factory S Emetine------ Good 0.00945 0.0106 3% 0.0116 0.590 Gelsemine---- Fair ------- 0,0096 7m O0-.0120 0.500-0.540 Hydrastine--- Fair ween ee eee ee eee oe ---- 0,476-0,500 Hyoscyamine-- Unsatis- 0.00698 0,0116 ----- ------ 0,400-0, 454 factory Morphine-~---- Unsatis- ------- 0,0128 ---- factory Nepalline---- -------- 0.01940 --<<<-. ««--- ih, SO CRR sees = «Ss @ os we 0.478-0, 526 j Nicotine----- -------- 0,00203 ----+- ----- ee Es ae ee Pe ne Pelocarpine-- Unsatis- +------- 0,0055 ----- ------ ----------- factory Physostigmine -~------- CRE DS iwi 6 die ie 44), SH4 548 a ee eee Quinine------ Unsatis- ------~- 0,0056 ----- <----- 0.299-0,.323 factory Babadillinee- «-----<-- @,@1870 ----<< <<--< s-nc0- ~~-.~.----- Sabatrine---- -------- OO ee ee ee Sanguinarine- Fair RiGRTES c4ad rene: solution, so ti ne€ i Cipitate, shali remain of a dark red color. 799 a474 Nee > ; at aA) oe | - 3 4. i . i aa lt 6 AV LILE, u LA Aj } i. wr) : =F 4 =) Gag & u = quar tity “ re) ; a] ; . 49 a4 F of alkaloidak solution to 5© 1Nn tne assa repeat the ex- 5 7 : periment, using 25 c.c. of the decinormal iodine solution, until the and shakin water addition of the a ztely measured dilute alkaloidal solution, until the diquid is perfectly transparent, and of a dark color. (The iodine solution must be largely in excess throughout tne work, hence, it L111 not do to add more of the reagent if it be found that the lantity used, was from the beginning). An aliquot part of the liqui tered o and the exce iodine in it termine tration with decinormal sodium thiosulphate (U. S. a) 1 oa > F - 7 ; Wy) } a ~~ ry =< ; subtract the number of c.c. i ro Oe ; in Loe quan- . a a : — J - so + . . ; = % . . a 3), tity of decinormal iodine solution required to precipitate the a | : a £A7 9 ad; wa) + “wa hexra . oes Bes a8 5 vhe alkaloid. 1e follow; cctors have been established experimentally. aca c.c. of the decinormal iodine consumed, te oy nag wit: 2 - ba) 2 (jA.2 . ‘ Se A 5S Freak wn : corresnponcs with ati OpPlINe, 5S. W4¢c a4 trvch ne OeVV00 ME.; prucine 6. 030 mg.; orphine, 9,4794 .; Caffeine, 4.85 mg. (19) 3 the metric nrocesacaes ot av he i 123. — ther volumetric processes that may be. sometimes serviceable, depend upon the use of Senaard Ilutions o some of the other precipitants of alkaloid ; which is very imperfectly precipitated by Mayer's reagent, Fb @ new hb titrated with @& Nenarhainte "O23 OQ} ~AAGA1W . may be titrated with Sonnenschein's reagent (sodium phos- phomolybdate), and this, indeed, admits of quite extended use. With our improved methods lowever, of extracting the alkaloids directly from the drug and obtaining them thus in @ pure form, these indirect methods of procedure have most fallen into disuse. ition.is to be us¢é exactly as May er's reagent acidul | (Hee or other acid) aqueous listinct pr ipitate solution, until it The precipita tration is mo loids named, wi Apomorphine ---------.0 425 yo 0 Berberine -----------,0020 Bi /~, Caffeine ~------------,00358 /2 .004 C een 2non fiC MOLL netine SF te : Nar ceine--------,0041 lorphine--------- ---,0( quinidine ----------~-,0029C Yo olla Quinine -------------,0027 ; 200448 ot ruchnine -------=== .00496 te opecia ethods of Separ Al Loids sf Purity. ne s oChe er” Proce >= Pr ] © aqueous solution with pho LO7% sid -01] uly re- pitate, wash with w 4 ite ’ 30 10% ic q i ~ 7 - ~ ~ aaa Caustic paryt ne re= : an pl - = + | 4 - y « ae a = 1 co ? a me ee ? of - action and distill t dbt any volatile alkaloid. If the alicaloi [a 9 fixe + ting rand nitosote wit x30 4 ALKALOLG LS » bow UL { ITSCLDLU GS WLULL CaUunulec lan - An om —) ] em -, = * ~ Daryta or iime @ 3 lkalo with chloroform. Hf MP = . f 7 A 4 Aaa 4+ +4 ig ia ets 126. agner' oy :- (21) Acidulate the aqueous solution wito sulpnuri \C ‘ecinitate the alkaloid wit excess of Wagner's r t. Collect the precipitate, dissolve it in a solution of sodi thiosulphate (hy; Lohite) Tats ivpend ex yr! (22)8- Precipi te the S ignt ly Besqul aed aqueous solution with an iodine solution containing 12.7 grammes of iodine and 60 ramnes of potassiu 4 teiie te "‘tigs litre. Collect the precipitate on an asbestos filter, wash thoro Tit s0ld w ter, issolve in a small quant ity 2 irified acetone, dilute w water and shake With light petrole (boi fi with aldition of caustic alkali then after renderin aC: with hydroc eid Parr tic evaporate off the ac: e at a gentle sat, add a few drops of sodium thiosulphate, to remove free iodine, finally, render the solution alkaline wit sodium carbonate or with amonia and shake out in the usual wa v 1 chloroform or other necessary solvent. C » TY U T) ‘ oO - ct wd fee x t Us per) a @ ~~ © Q ss o © tao oo . } -~ + 4 w= ~r4 ~4 4 . rr atc r a Mie os 144 Solutl1 Mn Or VOL Aone Ly Ba : Mave. p he e LAQUGS OUS Sol the washed iodomercurate init ; +o and Sl1]¢ - atc > solution and cai @ pot and then extract with en appropria carbonate be subst U L-£or caus aS e solvent). L129 AN O1 I Rr su TE withiodomercurate precipitate in necessary, and precipit ati: t he Phide gas. The filtrate ca e fre be desired, after expelling the excess of hydros by adding excess oF silver nitrate LVLeerL! Adcad 4 = Gav + Werineiic 13¢ JIA 4, / OC Lv _— a L > 4 u lrmug with sd wat earl eutral and p oh ZB Wits I , + - + q Wal-% a ; it ate the - ibacetate i excess; pr e E r { Lltered Lt. | aul 9artially neu > Yat ¢ Ty) : ‘ my omol; ight exce Olle 5 14 4 r4 y ’ A ry dic and nitric acid; mix the ist precipitate with carbonate of calcium or rium, or wit! alcium or hydrate, dr t Wi I manner just described; neutraliz scurately with J soda, a } 3g it yidi1 ex nd preserving e neutra r- of e solutio 5 uc additions of soda ; a wi 210id quire for complete precipit Yr nee of an excess acid;--aconitine, physostigmine, veratrine; a some may be precipitated without oss from an acid soluti this is the exception.) Collect the precipitate W * ' c . > - »~ 2 ~Yy* ly with wate dx Lt by OF ferably with precipitate e hydrate, or with zinc = ssive portions of petroleum benz xed oils, camphor: etc., the solven crystalline, capsicine, peperine ( urt ) IE : rtain c i (in part); (b)-- Amorphous, certain const: lleb ma proaucts of aecompositi of Ou. Kv ~ portions of benzol. Thi: | a si cascarillin, caryophnylli U L) s at 4 a ae ~a alla ~s3Ae > ulin, santonin, and the alkaloids, ca S14 | 4- ayes 7- , 7) 231 - TE with traces Oo of be ri and bperatrine: 5 124 Nerang 4 hat ‘aA Friuid new a. ws « ti Gay ul > VALU , u ame manner. This solvent w : ve Ol igitalin 2 “ —— oe ee . CS . ~ + oQng em an ) > [ = s ~ }~ 1? a ct } t physostigmine, and veratri2 substances imperfect Vy R La Text , it ce LSO. ext, snake the OlutioOnN once benzin CO Lenove Li TT I It n ALKALLN ; TL I Je jy (2) }: cy t 2. n c ¢ ‘ v—c_ coniine, lobeline, nicoti trimethylamine. the remnant partly J cinchon ct ne nepaline, thebaine it remrmants of brucin a , narcotine, piysos . ne. 13 / . a hs y} L Gi L€ Re J : } OT *) phine in part) 1 G i716 ; G ine eine and pap i A Alcohol j sALicin 301 ; YL 3 - ILANALI J re J senegin, morphine and narceine. The flui will still yield > chi rarine,. e ji © es? aa ae an mine vas a ake I ye lline ae reid “Ty owe 156. 'On Acetit 3 a Substitute yr Ethyl Al ) extracting the active principles oj ome offic Dy . : Ke R. Squib de ( ( ) In the proposed substitution of acetic acid for alcohol as a monstruum for extracting and a venicle for Serxine administering the active principles of drugs in med icine, the very first question is as to the therapeutic equivalency. That is, if the presence of the necessary} amount of acetic acid in fluid extracts, etc., can he 5 to be theraveutically aoe Age Beep ee or more objectionable then the nesessary amount of alc 101, then it is not proper to make the subd ry stitutions eti 139. But acetic acid has been used for the extraction of cantherides, colchicun, ipecac, Opium peat. etc., without developing any known thera peutic mal. onjections, and in a limited experience in the extraction of spices, and of some drugs for veterinary use, it gives extracts practicaie iS a gegen with those of alconol,. The acid has univer- sally accepted food value, not only as a hydrocarbon, ous as a mild ts AP aid in primary processes of digestion, but, in the small quantities that would be presen. in wne doses of fluid extracts, it would be practicaliy inert,or at least,,as nearly inert as the alcohol which it would re- place. 140, Its vroperties and value as an antiseptic, deter- gent and preservative are well known, but, whether it woulda he present in sufficient proportion to preserve sucn prepar ations from change during a long time, has not yet peen ae- termined, Dr. Squibb has preserved samples for two years without change, these being the oldest samples on hand. 141. Fluid extracts made with acetic acid menstrua are much more loaded with inert extractive matter tnan when maa with alcoholic; and this is a@ disadvantage, but harely hurtful, nor more than an inconvenience occasionally. 1426 In compounding prescriptions, the acetic ac 1a mer struum has a slight general i amount ef precipitation on dilution and on mixing, and in aavantage over aiconol 4 7 = 1 the character of the precipitates, these being more solu Le and containing Less resin and fat and probably less of tne active principle. In administration, there are simitat slight advantages over alcohol in that the dilutions with water at the moment of taking the doses are less muddy ana unsightly, while the acidulous taste is less disagreeable. 143, Prom these considerations and from all that is yet known, it is claimed that there are no serious tnherap- eutical or administrative objections to a more extended more general trial of this proposed substitution. 144, The chief, though possibly not the only reason for a careful consideration of this proposea substitution is economy in the use of alcohol by wne use oF cneaper sol- vent, The alcohol of the U. Se. Pharmacopolia 91% vy wel costs about $2.40 per gallon of 6 lbs. 13- ounces avoirdu- pois, or, say, 35- cts. per avoirdupois pound or, say, ’7- CUB PS aE 1900 Oma tic acid of the Ue. Se Pe 36% Costs abou 10 cts. per pound, or say, a2 Cc tS. per 1060 Gine When di luted to a strength of 10%, which is the strengt most ire quently required as a menstruum, the cost is less than o Cs per pound, as_ against 18 cts, per pouna of luted alc of the U. S. P., with which this 10 per cent. acid corres- pondas-- The alcoholic nens tru costing six times as L tO acco iolish the same xtract! L ON« 146 In order to measure with a fair degree of accurat the conparative FapAc Lt} ad alcohol and acetic acic or ex- tracting the ctive principles of drugs, parallel extracti< or the rug were made under the same conditions and < the sal . i Vomica and cinchona, being to ext ere used in the work. The n No. 60 powd the alcoholic extraction i Oars for the acid, The repercolation process - extractions ,and siphon percolators, and an ead that the mass of solid contents was ke Foe with the menstruum, as indicated by « stratum on top of e mass and the percolate rising in the well tube to near wne level of the menstruum on toOpe This mass in saturation, was allowed to stand covered for 48 hours, when the sipho was put in place and started ,0 only from the upper part of le rate of dropping so slow as to yi ons of 100 c, c, each, in the 24 ho 48, The results of all the work showed that the ace% acid extracted the drug in a much less time than the alcono. and obtained a higher per cent of extractive, Then, by the substitution of acetic acid for alcohol, one half the cost of grinding, and five-sixths of the cost of menstruun are saved, an equivalent product being obtained in larger qua Clty. While acetic acid has not been given much show in egular fluid extracts, it is now employed to fair extent in preparations for veterinary use. 149, Assay oi Galenical Pre 20araviongss- Fluid extracts To ascertain the alkaloidal svreng t O23 we J iid extrac 4 ve may generally adopt one of the following general methocs of which; some, as (a) or (f), are recommended for usual routine; some, as (bh) or (j), are o: limited utility. (a) (Prof, Lyons). Add ammonia and shake directly with a immiscible solvent, wash the alkaloid from this into acic water, separate, add ammonia and shake out once more wi she appropriate solvents (pb)- Dilute the fluid largely; with water ad excess of lead subacetate and filter; Ada sulphuric acid agrop by drop to precipitate excess of lead, filter once more, concentrate, if necessary, after renderir I +e neutral, add ammonia and shake out with chloroform. (c) (27) Add to the fluid extract, ferric chloride in ex= cess, then sodium pidarboenate suri ‘i¢ient to P sea: a stifi magia. Triturate this with successive portions of chloro-~- form until the whole of the alakloid is removed. This may be suffici ged pure for weighing, but usually requires to be washed out with acid water and extracted from this once more hy adding alkali and i out with appropriat . ante ad) (28) Dilute fluid extract with equal volume of water to which Qe. $8. dilut. acid have been added, Riv ap- orate off alcohol on water bath, cool and filter; use li- quid either for gravimetric or a ak orator node (e) (29) Add to the fluid extract, ten to enty + s its volume ’ weak Prollins Mixture and shake togetner I! 12 LING « Pour off an aliquot par’ ol Me ELuerens 1 cu ia sr in the assay of a drug Prollins Mixture. See(160), (ft) (30) Mix the fluid extract with oak saw-dust, dry at a low temperature, treat the residue exactly like a crude drug, with Prollins Mixture, etc, See p. (159). (z) Evanorate off the alcohol at a low temperature, aca plaster ot paris mixed with a Little sodi nLcarponarve, aLtow tvne mixture to set and harder ; and extract the alkaloid simple maceration, with form (mixed), or other apy must be purified as in pr¢ kaloid directly from the an a. | ahatvdan- A14 ” y agtran s$o0aa ; ana SAacKine eut Preneave i athe YO) re Pala. eT, 1er I eryo © iA CVU UD > + of equeous Fluid containing alkali by addition of of paris; the ethereal is * pitrat P with centinormal acid, Ors The method is not avpl: ils @) salts of ammonia are p ‘ Ci}. Add a little water and evaporate ly dryness, make up ° suitable volume and titrate yer's reagents ct in mes 1lts voLume oF, pre 2 the alkaloid ltrate, ng emnonia, colle dry and or else, after d os riate solvent. Rvaporate and weigh. (k). Introduce the fluid extract without previous treatment into a perforator, render acid and wash thoroughiy with petroleum ether, then 1 a - 4- render alkaline and extract the alkaloid with an appropri- ate solvent, (1). Add. to the ract, a few drops of acetic acid then an equal vo} iter, evaporate at a temperatur not exceeding 50° pell alcohol, remove « oropny tl etG., by repeated washing with petroleum ether, recoveri (xa) > Put int > & vwo-0Ounce y Lal > one ram oj res i. hs ee Aa Lime, add 5 Cc. Cc. of fluid extract and immediately 45 c. c. alcohol, shake well for a minute or two to insure complete solution of the alakloid, filter, render faintly acid with sulphuric acid and filter once more, evaporate off the alco hol to obtain an aqueous aratively free fre inert matter, from whic! lay be extracted, after washing once or twice , oy renderi alka- Line and washing out in ! = o . x © Se + ©. 5 nearly all the alkaloid in acid solution in Nog 4, an ac kel ) sid fluid containing a little alkeloid and i No, 5, water with possibly traces of alkaloid. Now, add + No. &, twenty Ce. Ce of chloroz orm-ether, (pure etuner, 13 ¥.21i8s Will answer tne purpose) ana @ lew areps veer 1 me monia, shake well, let separate and transfet the ethereal fluid to No, 3, Also, add to No, 4, water of ammonia, in excess (15 drops or more), shake 30 seconds, mak ing sure +] ‘ vy) a io 1 4 1 os + aft } ‘ ° 5 4 ° 7 . vnNe armnonia 1s in excess ( Wetom VGC Y¥ APO! Wilumlt I! ed = i VILA paper) » +-ev separate and transfer the ethereal fluid to + fos , Sm ss a ny ‘ yf a £ smmnys ¢ ys } co No, dy VO Which a ay Op OY two oO} Wave] OJ ammonieg Nas ee; previously aB2AQACH.s = nah, +} cat emten of vial : : L526 Wasi Loe COentents oO] Lie VLIALS No, + Ala No, ) (in order) in succession with two or three fres] ortions 4. 1 . LALLS of ether, making sure that all the alkaloid is extracted. Pass the ether in each case, finally into No. 5, which 7 ot ’ ~ oa ‘ re ! uP ‘ " 2 [an do ln 4 ow P - 4. mn erves me rely as G& WaSSL DOVLLELE , ena 3! ror Lois , arecer come " 4 . a — s - a —. 7 =e : x : : PsLeve senvaera wl Ost Lnteo a tay CQ pcakel ; niet Vii bOll e y? is ¢& ai ae . 4 _ -— a — 5 = = = on + Ta a a ~ : + orl Val orated to dryness on the water bath and final: VELIZNEAs Where chloroform has been used as a solvent, redissolve the ‘esidue in alcohol and ep again, to expell th traces of chloroform, Pinally the residue may be ed in ether, or in alcohol and the alkaloid in it with standard ac id. 7 22 sa) ae - saisitai ii alia ani toes a oe - aie . e eee 9 a+ $ L555 The above precess nas Deen piven in minute adé@étvali.a | an x . . 5 de = 7) expen mae = oe c at mM yen ~ hecause Prof, Tin ON CL1+AIMS 16 aALWaYS ELVEB SAvLlsLactory re=- SULTS. Frulsionizing is not liable to occur, while the 7 An Ares Avy > aT +lp $A y . sa naytety vy ether-chloreform removes the alkaloids almost as certainl: 63 " \4 3 mHninwrnt sc . . ~ we - V “ Ant an e aS ne pure chloroform does, It May be necessary some- 4 3 a hw an oe ie re A cr n vimes, to carry through the entire process with ether-chlor Lfarn ath ag a + «re a ; } ~4 = = ‘2 ah Ar at ArT ) ~ i+ Ol OY m, Ol »Q ar Lt S us ALLE, pul © chioy OL Ol w\) Ce c.) wn t- | 4 wee + “Hh 4 ee ann 4 . 4 i¢ io ¢ ls a ; 1 “( Ses Liars asNn ing » BQQ1INE AMCALALE LY » &Lnel enougn (; 10 Y oF " i wad - * oe ? a ~m © “ime _ qa . = ; — al =) ' ) Y~ WU a ~ +< alll : = » Iw 4 ) (151) anc .) . abbrev yllows. Procee | pefore, up to the point wher ereal solution is | treated with acid. Ins ( a into B& third 7 collect ti porti ¢ Yeée OPw@o2on J ealcey evaporate eat 1 ryne and determine the alka- loid by al (90) or (91). Subsequent separation and weighing 0: be made, if desired. Ron. The ac 3 mtained it lals No. 3 and ia, 4°(291); ¢ i "al rendered alkaline, and the < 2xt 1 (5 ), without ald any prelim ar T Lé - er. 26. ut it iter P ( ) a solvent has a hig “ ay ce fluid - ex-~ : tract (e.¢. pure lloroform), a plan differing in detail . must be adopt« j-"P 10 ec. Of the fluid extract (: aller quantity. if it is rici in alkaloid), id a tew nay 2a CeCe chloroform, agitate : 4 little water (3 to 8 c.C} | agitate once more et separate a off the chtorofor into a second separator ed ter to whi ; been added a few drops o alba id (125), ag- itate and, when the chlorofor ? te raw it off into a 3rd separator contai a Ge Lat woter. Agitate and separ t he ro oul LOW tea no traces of alkal ( 3 by yrati ew drops on @ watch crystal. a ; : nd testing with Mayer' tc t}). Treat the contents of sep- | arator No. 1 with |] Lie. lorofor which is to be passed throug the s roce { repeated as | rom No, l. t Lov. len Lorof or é remo ! (it is to be preserv "ar t tion) ut into ep- arator No. SC 1 a few drops of amonia. shake togethe1 lraw ot nd aqueous fluid nt y into No. 23; ack C Shake together, 1 Oo 3 in which ] ~~ 3 ae ee © 4 , ae 1T VLOG COU ert ¢ ‘ chloroform, passin, tared beaker. % on water ; dry completely an by titration with ; ne modificat applicable to thi 158. let ail pott omec porce Ov earbonite, with co sults. / roform using each making up, in equal portioi VDSvIracvu | ) - f fe) he fluid extrac add° an equal mixi . lay +4 iu { e e ‘ -- Wo Ul b) , | ¥? 5 } { [ : rT rT) on * 4 + ry ’ he 1 ol Lriud > i ~ 4 ~ y ~ A. =| - ! Lf € oro] i LY Ode I iL ¢ \ . vd } } ‘ iy | ) CLa*L PSs CONG , 44 ] + 4 - ne TA * H eve ine tine alkaloia / — — i} - my P rn e 1 Ad L (< 0) ( ) e OF CO i © 9 \ , d ) : oo . TT ” 7 T+. e O at ° J * Ue L ! ae k ; = 1] a ) = ' “~ \ ‘ ] ‘ eCe ; Ce i> 1 vere rte Or Lron ) wt @ 2 t €) t ree kt aa ; ( Ld QO ¢.c. Divide into two WltUn. Spperical Di j Gt Fee ,.SUeCCEsSLY' portions (10 c.c.) ' ey Sulphuric Ld. Go y solutiol In a second epa) OO] ake alkaline wit ONL< wash out the alkaloid, by rotat etter than shaki wit | three sucessive portions Salts. srofon (10 oe +e it raporate the chloroform i ar nstant weight and dry & weign. (7: Ll portion t ri ] Loroformi extract may be used for an independe Lx leter- mination. ) 159. Detail of Process of F. A. Thompson, (149 f.) Place in a capsule, 9 wv ; é ew-dust and be Ni gradually into this, 10 c.c. of the fluid extract. (If it contains more than 1% alkaloid, dilute with 50% alcohol to reduce it to approximately that strengt and, take. LO..¢ aCe of the diluted extr take af rse, exactly how muc ‘| this represents of the original extr -). Mix thoroughly wit the saw-dust, which mu icient quantity tc sor | tne fluid pretty wel ry at a temperature not exceeding 45 aecr es e> transi er 40 A. @) > pr =) r ipt j [ L F LOW @.6,. Of modified Pro. ixture (13), shake frequently during 15 or 20 minutes, ur Oo AChLY..OM .C «Ge, Of. he ethereal fluid and complete the assay exactly as described 11 (62) or (72). .This method 3 rteinly to be preferred tc | that of Steizlitz (149 e) in which there is some'difficulty | in deciding just what quanti £ the ethereal fluid should | be taken as 2 e e i (¢ e&e ONE g ] ) of the. fluid | extract taken. | Loo. EF ean t he has someti pt ec & plan similar to that of Steiglitz, for rapid approximate Work, @s follows: To 5 ¢c.c., of the fluid extract, add.5 c.c. of anmoniated alcohol (alconol ine volumes, stronger ammonia one volume), followed inmediatel y 45 c.ce ether, shake well two or three minutes, let separate and pour off the whole of i the ether which ma € assumed to contain 95% of the alkaloic present, and is to ; the ordi ry assay Vv Prollins mixture ( Ley lies “i4€ ‘on ( 50) et sé Cs is vrefer- aplé in that it does not consume so much time, 16lL. Other absorbents peside saw-dust ave been employed; absorbent cotton by some infusorial earth, absor- pent paper, vegetable fiber in the form of twine cut in short ha jieces, etc The saw- t seems to fi bine requi 1 best of all for reasons that need not be enumerated. Care must be taken however, in selecting a saw-dust., using one containing as little tannin as possible and one as free as possible from solubl wtter, particularly of a resinous | | nature. lence, pine saw-dust j t+ to be use nie first extract« Wit LOONOL.. Well wasne sowedust fro hard-wood of any ki : i : < = ; —-_- — @) NS . + Cc t 2) ,. however, be too fine. Filter paper is liable to soften a mat together, but if cut in small pieces and used in quantity | icient to absorb the inixture without bei uc! soitened, it answers a good purpose as oes the chopped string or rope. Sand or prok cannot be recommended ; pumice-stone broken into fragments about size of hemp-seex is better, or \ 1er absorpe ee eaeraee be: pe necessary to in the prollins mi> Hoth: alkaloidal salt 263. \psorbent following manner: four ounce round soi two grams of absc by means of a pipe rich in alkaloid) ly absorbed by tise modified (13) and hen take out 164. Kep 3 the fluid extract quently during oO ars. 76.6. Of. the fii the usual way. Put into a separat of the tincture) of alcohol, add | end 50 c.c. of etuer separate. Draw o. add yd the contents 90 grams ether, shake: let senarate and ar: the eral of the Alcohol (25 a.c. e 9 second vial with flask to which has rator. ‘he ether water by shakin then filtered into of distilled water is washed like the to wash the flask filter previously of the ether. Lae mal acid. using as .c]l, time ~ 3 golution of iodeosi! 166. The met! of dispensing wholl; point in it is present in the ti Laid . The etherea out harming the al the titration aft« more conclusive oo process of its one a6? « Tinetures a fot] y sot acids, must pe dé Wie (? i. @ ther ; (the L raloid ) water during hours fi further washed once wit etr icidulated with sulphuri wovod ‘ ey j cner to rel e traces of these objectionan1 Les. -6Go.% 2f the alkalo ot easily so te in etner it is necessary to use, a solvent, ixture of chlo ox and ether Three portions of the solvent are sed. of re- spect ively B)..) LB. d Cs t+ these are washe >t with ure water it with a 30% solution of sodium chloride, since With pure water, emulsitic liable to occur. f 169. Tinctures, wines and elixi:z re to be treated in general like fluid « 2 ts, G tne olume of fluid “LY pe generally reduced con er wit it age y evapora- tion at a low temperature, "eliminar step. L7C sy rus YS rnay 4 Some cases DNC ass =1@) Vv Ad ing al kali and shaking out r T } added to facilitat« . 2 essary to dilute the syrut recipitate 1 a Wagner's reagent and recover it from the 3) BMiiso Solid extracts é NnveE n 3 tracts by dissolving in dilute alcohol where that is practic- able. In many cases, t ber di ‘ a, whole and in such cases, special precedure ist e used to obtain a solution. Lt the dilute alcohol yiel turb id mixture having only minute spended ]j j olved matter we may sin p15 r add sawdust mr l oroce rai o (159) L 12, ° ee a an XC race oO. C5 lé Age Se loaded with gur my matter, > maj 1 t Lb. lcohol accordin to tne foll wing procedure:- "reat ral of the extract in a beaker with 5 Ce oc. dilute alcohol lad c. strong elce hol to ‘are ipitate t] tir until the gummy atter sep- arates, decant int« Lal re-dissolve the gum in S=-5 c.c. water, add alcohol, dro lrop to the oint of incipient pre Lt : the LO ec.c. stron Leohol to eeeeer carat te t “um . t is process once more, if lecessary; (test the gumny ue for alkaloid, by Mayer's r crane ). The united alcoho! trated bj traction of ow be concen- » solution suitable for ex- A¢oa. In thence alcoholic extracts heavily loaded wath chlorophyll, fat or resinou tter, the following method will be found a go » Soften the extract by warming in @ beaker with a little dilute Le Ol. Add to the syrupy extract afew drops of dilute sulphur; cid al treat wit successive portions (5-10 c.c.) of ether. pour ese off into a separator until the most L F1LL5.ebG.. has been taken up. Pour into the separator Ce water with five drops of 10 ri id e,let separate draw off the acid fluid into t c ' yntaining the residue of the extract, w will now be almost wholly sOluole in water. temove the solution ) ratory nnel , wash once or twice wit r ether to remove a ry chlorop! yll still remaining, separat« ender alkaline and shake out with ier or so { ! | || L'v4. eT 110 ( Lg ie extract i! QO oi cian water contains ; LrOops \ f sulphuric acid, ada Oc.c. solution of lead acetate 10%), allow the precipitate t<¢ settle and filter the solu- i Uu . 4 Pept ant zg smite —o a . on @asure OLL 10 Cee I LOE LTLltravce a2nhvo ¢ SEPaY Lory chloroform 4 volu nd water of anmon rolume. Shake well for a minute or two, ke up the ether-chloroform layer to its original volume of 40 o.c., shake again for one minute and let separste. ivaporatvec 25 c.c. of the clear ethereal! solution, representing one gram of the original extract, = f determine the alkaloid in the residue \ Wis ye BIG ¢ Method of E. Di i (3sjpre Mix two grams of the extract (1 cram in case of nux vomica) with 3 c.c. of water _ “ add 10 grams coarsely) owdered lime lime formi 4 crumbly mass which is introduced int lisplacement apparatus and extracted with ether, of which 80 grams may be used, The re- percolation is continued from 30 to 45 minutes in case of aconite, pelladonna a enbane; a Qu und .& hit ain cease of nux vomica. The ethereal solution of the alkaloid is tranesterréd to a tared dish or peaker, the last portion bein rinsed out with 2 litt ‘eshvether;s Locpeg OF distilled water is added, and the ether evaporated at a temperature nat exceeding 30 degrees C. taki re to avoid proximity of volatile acids like hydro Ci itric or acetic. The residue, weighing 1. issc 5 CeCe AlCtO= Meee GOscgr. Li882, LO c.c. a listilled water added, and the solution titrated wit rial acid ising rosolic acid as indicator. 176. The metnaod just describe 23 been justly criti- cized owing to tia fabili loss of alkaloid from the action of lime. [It ertainl no advantage over the other processes gi ‘ nee.)6|6Method of , Beckurts. ([{ ) The original process consisted in dissolving r % ixture of alcohol 3 6.c. and water CoCo, ¢ 1 c.c. water of ammonia and shaking out with three successive portions of 20, 10 and 10 Gee. chloroform and determin the alkaloid by alkalimetry. In the case of extracts containin; lorophyvll, he now advises the following procedure (5) Dissolve 5 «grams of the extrac Oo ~ 4 ano: G@sc. 0 nognol »apecr. O.89: ne baryta water to make up volume to 150 ¢.c. allow 1 leposit, fil' precipitate excess ol ary vy carb dioxide, Filter evaporate 75 c.c. of the fi “ate (equivalent to 2.5 grams of the extract) to a syrup ‘isso e j a mixture of 6 ¢,.c, 1 i water and 3 c.c. alconol a 1 cec. water of ammonia; shake out with chloroform ; abc Al determine the alkaloid alkalimetry. 178. Method of O. Schweissinger and G@ Sarnow (36):- | “ou Dissive 2 grams of the extract in 8 c.c. water of anmonia, shake out with 40 c.c. oi ture of chloroform 3 volumes and ether 5 volumes, Let separate and, after half an hour A pour off exactly 20 c.c. of the chloroform ether, correspond- ing With one gran o the extract; evaporate and dete alkaloid by alkalimetry. Oodvi sly the method cannot be used t - without modificat camini é tains C = ~~ I ™ “ 4 7h oa cli oO ~ Oe ea. Np Dhyll. LONE TW. ye, We FQN jel NU: © Of Fapl Lit. € 2 OF ‘ a [. M. Gor Bye tates that. fro ett sal poin ) nme o > eat i ie tue 2st met estimating alkaloic g loubtedly the alkalimetric es saan Of their basicity. The onl lrawback to tii et e olwavca be . + + . 4 tinge gan itr ‘Hn Nas always peen wne ig t that owir CO 1 S pasciLiey .peni very weak, the acid compineda regard to most indicators sharp and distinct mhuric or hydrochloric acids aw ~/ - OG San ade a-- re Wa) : Gefiniteness of the end 1 as not ” 3 : “wr 744 = + 5 mn vA eee LE35S Mevnoa O12 Fer 4 L¢ } ) } ° be LOLLOW iD “= simple improvement makes i ossible +4 2stimate all sal forming Alkaloids wit roneé T 2d inorganic alkali } ( phenol pht nalei sator J hoe etc. are apsent. 3 20 the alkaloid after ; een 1 € - 3 . srl 4 . 7 | Be andardized miner Qc } 3 ¢ | b the alkaloid always sé rat is a salt and therefore ta up an amount of acid which is equivalent to the combini weight of the base. 1 ture to a certain v ume, shaking until t { tate separaves out ilteri aD > 1. — 14 - ") - 2 75 “7-4 4 4 ; nd 7 5 off halt, discolorizi ith soluti ) 300d Chiosulp! in @ase of Wamer's rea uy, \ excess of the acid can accurately determined by tne id of standard alkali. usil phenolphtnalein as indicator. The alkaloi Kigee CE moved, the estima san be carri¢ with the same s ness as is obtained i rdinary LIMet ric rlysis. 180. In order to obtain very od results ie acid and alkali should be standardize ‘or each alkaloid, bj weighed out sample o: caloid and proceeding as ak LJ r . «pei i ; a ie ate 3 ot] 1erwise > LOE f i t 1 Ta, ie 5% L€ > ) Le m1,4 Ae As rm 4 a 4 + 4 es ae . * * thas 15 aue to the } G haa G i sence oO orcan] ter some iodine of the potassium iodi P the reagent i free and an equivalent an t oO sid disappears. Thi: be proven by dissolvin some alkaloj ead water O : Ce 4 = 4 1 4 Fe) is adding a little ] hours. If the liquid be then tested with starch, the pr of - . - } of method is that by precipitating the alkaloid, a good dea of foreizn matter whic! enerally acco mies alkaloi these are obtained from extr ict or tincture i, Will also thrown out, the excess o +7 “emainin i 131. . ‘ | LG ethod of Prescot rordin,. alkaloidal “he 4. a alate sh ash -. ™ ny 2 ee ae — " DULL always repr esenting , GeLrinite, quantity of..drues 1 saaxrar . Ss oe A eT teal 5 R ag aASSayean LS poure SLOWLY an T sonstant stirri int re) { Las I mae Ln LU a we i : , % ! free iodine can be e: s110WN. Another advantace oi solution obtained by whatever mode of extract - 7 a a - ol- ate e arp= “ rae ¢ 7 : 1 ; q 1 . . :] a TD mn a. ba i >, > Ol Ms ole wks WA Xe AJ o LQ ‘« « Ne Pars a5 € - until the veriodide nas sevarat Ge tne supernavenst Liquid x: r-@e.c. are then iltered off and i} hi Jjortion the wn ctt y pa 2 e€xXc : L thiosulphate. e's le consumed mit Led y the pror GU Or 3 ves the amount of alkaloid present in the quantity of drug % er. 182. For accurate, ex ijent a sheap 3a it >) \ fluid extracts Tagel (39 ecommends the following: - 1 9 a4 porcelal Mtoer smal ligh, 3 21 s of the f transfer to a ined ne 9 le o wou, LOO egcy Capaczty , f moa OO C.C. re ethe: ule é small quantities at a time, LO ustice sod verifying the alkalinity »% itmus ps rand avoiding excess. Shake the contents ke tle vigorously for @wminute or 2 and add 2 grams « powdered tragacanth, hake a again for another ininute rive é small globules of traga- canth mucilaze, ime to settle scant. 40 c.c. (equal to 2 grans of fluid extract) of the clear id into an Erlenmeyer flask of known weight, distill the ether, add distilled ether to Gommon stock, dry the alka at about 50 degrees C. in a current of air, to constant weight, Multiply by 50, to obta in the percentage and t assay is finished. 183. If a volatile alkaloid be present i L will ,; generally be noticed by its odor, at whatever point o: the operation it is liberated from its combination, by tl alkali. Should its presenc be Sime detected or suspectec it may be conveniently isolated by adding excess of lime or baryta, and distilling the liquid. . e alkal loid can be fix- ed in the distillate by : i a slight excess of hydrochloric acid, and after concentrating the liquid to a small bulk may be liberated by addin; large exce; of caustic alkali and extracting b) gitati wit ther, 184. All methods in which an aliquot ] cible solvent ist en to represent the corresponding aliquot vi part. of the dri or extract, must be taken as only approxi- mate. The pr actical man, even thougl emist, is willin; tO sacrifice exactness w roximate results can be reached without expenditure of time required for exact de- t eryminations. foritcy oO ists prefer plan of dissolving extract in dilute alcohol and if ‘easonably clear solution results, treat as in (150); otherwise adding: saw-dust after the method of Thompson (159). When the extr ack: contains chlorophyll. the method of (173) is prefe: le, althoug] extraction with acid water a iltration will often give a solution containing the whol th aloi which can be rendered alkaline a sale ut with ether or other approxi- mate solvents. ? Te oe ly dark brov ' Lt lL eG i Ww ort i ‘ be fl + . 4 - , + . st el cars rls ) L€ i OUd UU - ij —- . i 3 ‘ i } | } | Snore pad 9 \ Lhe ol po . I yooad 10 +7 + + ~ aA tex] £aaiiof +. 4 4 Os and Fesinous, wollte, geray.2li , Y ni ULSSUES Laste } rSG ; : - : “ie ee oe ia ak ee ; m liar tin iF Sweetish, the acrid and tingli aE 3 pe sensat i > tong L acteristics upon which the toxicologist depends for the re- GO@gnition of this drug and its preparation, At the upper portion of this drug root, Ut rojects a later prancn connectin; 2 ] C r W Ls an OLispring o 1 Other. exce unstable bodies, liable therefore to undergo changes in the - : o “ } ee 2. rocess of extraction, eve Jueted wit extraordinary care. The rincipal mstituent is aconiti - » 9 >! 4 4 1 4 : ea 4. Oo") J 2 } - = ‘ Vur L mh . i 5 Ov P mn 2 : 4. ‘ E ~—o 72s OMe _ - QL § LS white dL l } . { Lo 1 3) Lt 7 > be Obtained in rhombi ilar ory : ost insoluble i Gold water, , $0 Le i Bae 7. d di te acids. the most recent resear ] 1 Ummne?} val indicate the presence of a ine apuline as the remain- ing alkaloid. of aconite. How r knowledge them is not SavlLSslacvorv. co n a ¢ ra f ¢ 4 = ~ 2 ry ‘ es) cr ' = LN oH > i?) i Cc lan) \yv ee : best is the followi: mY Yau y rhaust the powdered drug - 47 ywrrla+ aln f " ’ : . ( OVC) "W Chiorot - - -- --=—=-30,0 i ley. it Ammonia-~---- -_—-— _——— ee - o\ >) ( hi at ex a Oe ae eR ee a SY SS eS ay ee Se iiieiontiandieniantnen 1,0 = NO " Pour Off ~3-------------- ~_—— ~ —_—— — ~ 100.0 Thay w> of 4. > A / iconite Roo (80 1 ) ----- ——--=—=--+-- -_——- . Te teh bbWle anes 442% bates scm 5 R..ga tee * Chloroform ------ oe a a a ee ee —-2! " WRF / 11 ’ — i as ee ee = slay -10 " Vater ONE) Biase wie 2 7) s 20 " Pour off -«+222.2 «190 * xtract wit wdaro “ié 1, eve oro= - ay > } + ~ , x ; 4 IT w" form-ether Yr, Yev_tvel { et ls A l - 1O Ih ef! the tubers contain .6-l. + aconitine, Five samples _ = _ . Qe r ne 2 examined |; Ve . Pa We ) u - + rye - 4 4 = * ~ ~ ~~ = 4. easier WwW 0 LX Y a : LNnEe 2iUEe Oo any preparatl1¢ Cc J on the ner ) t ¢ ips. The test ylic in the following ma ri- [lake ur 1ué6o0 olution repre- senting in 200 pa le LOL contents of 1 part o: the drug. hus, a fluid extract would be diluted 200 times with water, containin; ittle hydrocnloric acid; the alka- loidal residue ' ; x drug would be dissolved in a littie a ‘ew drop xf dilute Lrochloric.acid (to decided acid reaction) added, and the solution made up with water to a volume o OO c, a 195. ad cue) 7 llowed t “a t, a: a L1f a a = — - - : “ : = A " 2 T> , 4% - - - 190ur perore roceeding to the actual test. Put inte B 25 6.05 measuring flask, 8.3 .c, Of the above solution add water to the ul j king. Rinse the mouth well with water take into it one id ra this solution and hold it in the anterior part of the buccal cavity one minute, by tne watch, ect t - ; 1 mm and rinse the mout once more, In afew minutes is the root be of standard strength, the tingling se tion characteristic of aconite Will be perceived in the 1 this will ntinue 30 to 45 minutes. 96 if the effect is ter-or i n that ex- pected, a trial must be e for the second time "ter int erva a ( Yr IUTS.» al the relative tCrenet af 1e NNR teh GP eae wig! . 2 pooner ge a ; preparation can pe thus judged after practice, with a consid- erable degree of precision. Different persons, o ourse As sae : 7 ~ “ . e : f 4 = 4 ‘ @iffer in susceptibility so that eac ust work out his ow 4, ' - c © A - . ‘ } " { { q Be VES I C1aom use WVaNla~vavdl : ’ ze a - i t v4 70a ; *. . 4 2 a ss hi i is nd 5 nite, 1 Lé é standardization. : 4 ~ o awd + es 1 ailmuch s x oreporti " -—a 14 ] +} . 4 ‘ 4 1T11En7 allkalnidae Ve OL PE hm ee Aden a5 wu na wd ~ ‘ - 4 . u w ws } = _ “ S . j | ey ye £ = , _ claimed by some to Keller's method of assa Aconite Leaves a0 DMEWaer se=.—— =~ - on sp Me at od ee ee ee ee 00 tt Colorof orm--<--<--—-——~—.- eee res). 1" A Oni a--—$-------- me ee ee aie ster tl) sls i OP. erp Aen ons O " Vater-- Ae as Se ew we ae ow oe _— vaovas = ae a ee tl Po a —--=----100 t Axtrace with aya 4 ‘ L ina Ly 7 thloro= form-ether. Decant 105 ezrans of the deep it to settle for a few moments and then transfer 100 200. Cormercial aconitine may be judged by the physiological test, ANCLLON remeay which sv and resin, This l rOz ¢ ly ¢ pl QCE - or + Le A a A a on “oe? TY be Le) A Naas Croerl Orme, aa n amp U 4a or tne r= | >t atlas - 5 e | ( re € CACLLAaACV D € Qice TL $ , Lag ( I wud mluQ NOv as nana Can lace almost m a J, O rua? etailed 7] PALLEG <- ik ae AVOLICaAL a @ | om Leeli } i) Par) 4 o 20 rie YU aci ed i ote Fate I 4 mA a WAE LLOQ L1LGU4Q Wa vii ; . c ro.) £ ©1iG ( aed ee tT Yew € ~' — 2 ; Lea, Jy © Scr 1 our 1 + Pp ae iL Ye a Ae Q r vy" rns : c lv acco . Lt ©. uP - Nr tg LOS J ( Wr . a , D SCeSsahe ,CQ O J er lL ceompm.let + . “7 = Li et ok ( Ce Ue eciaea Priddc By LOALS me Col ae ee JLLOK ve rr CrmoVv rv) Nem. O7 i SLOW LG ‘ ) 7 nJj.O Ce LC ¢ & § t & J _~ vILE AJ y ‘ . cl \ Pd P= rs) ] J Ke UOLlOL OLili 5. é “ 4 lire } ake Lot @ 5 re | on * e ( = Lio ‘ E i Ly 2 é . a SSArYV. y & hee ao er 5 some- 4 iA WU L YY) ) > om x v ALi i Fc Fe R —p -/* . @ 3 vl k a? r se , view of comparing the official ethod ¢ AS the modified process. as indicated a ve show that by the latter Milaehner per cent of alkaloid is extracted, the differe varying from .02--.04%. The British Pharm, metinod as it = eT ee ae, ae “een ovak a ? : oe B As 1 ! mae stands is also oven to the possibi i error to those hitherto pointed out rig:=- that a small ount of alkaloid may be lost through failure to obtain an absolutely sharp sep- = ‘ : fii aration of the immiscible solvents. With some somplete sep aration may take s | as wit uch samples, there is always a temptation t irry t ‘ation; a fourth tréat- ment with chloroform wil zlnost invari: > remove a further small amount of alkaloid. Hence, it is apparent that the 2 “ — o rs ae io adie " - ‘ Soa . ae we = - oe aaa ae = ~ removal of tnose substances IC! Cerrere WLth ext Ctd 2. . . ne a ns = EL age yes a me aren Sila 1. by the solvent and favor e sification, [ll generally be attended by a slightly hicher percent especially as under . t- 4. a4 R11 _ 1 c -ac 4 a | a, t< aPA ly. 14 art«) liadoc ) . - A l . ° \ Wak 'eh= u LL IIA wid ’ L e 1 ‘ LU Ly rocn ) LC LG - shake with two portio O forn { 8 (ei, cedat wi alkaloid with two successive rtions ( : teCe)} 0 acid water, and treat the aqueous soluti rice with water ammonia and chloroform (! 3) Getht bain thus, . finally a solution from which the alkalo: Ls procured by evaporation in sufficient purity to wei ‘ 229. New method of Ass: ' Fluid Extracts Belladonna Henbane and Stramonium (52):- Two "ans of absorbent cotton are firmly packed inthe bottom of a 4 oz. bottle. The into the centre of the cotton, by Koren ) j tte re placed 10 c.c. of the fluid extract to be examined. The fluid is | allowed to remain until it.is 1 To taken up by TI! ‘ + J | ton, and then there are alded 100 ec.c. Prollins mixture ne c 3 ture dified (ether GF CGQaGe. loroform 90 «a,c rleoholL 25 ea.c and ammonia 10 c.c.) : apout 1/7 2ur . After thorc ly shakil the 7 4 tw ‘ =m af ie = | ‘] are poured into a beaker nt aini D> O46 lis hich has een re ‘red 1oro Tr acaa byw a solution of i in ~, + 4 - * 4 , a | pl. Ae ws f . JuULY L v © ) , eG { ~ a 4 . . 4 ” . Into 2&2 sea Ub OY ] : Che peaker w 1 sut tie = A. 4 4 . 4 ’ % ar ig c , > } bd ad Qo c STL ENV aver IG aer wo LOG TL) gh Le Se LAS . . rt ae 9 ) S i WALEYrY With lO Lan = ammonia water to render the 3 Liquid line shake Out with 3 portions chlorofor Sa Ls CeCe Yesp. ivaporate the chloroform s a ry. to constant weight at 100 degrees C. and weigh. OF D Bel: P ters (538) i k Xe foerk p a pro ow used for tue assay of Bella- lonna pl is fToltows:- T ei] mina plaster « thie TT CG 2 1 be “ . er @ A 7s wD L v Lv Jiz UC dis = plaster It is wed by inco2 rati 6) t he extract of belladonna with 40 ms each of resin 1 soap plaster } r ams 1 aiker aa sai “ee, ae = ° m | ~ ae =" 2 2,4 Iu 3 ) AG! Le ~eve / WG l 6 4 LS 4 LSt« Lt e) Si VS , A LG ~ — ae ac + : > “Oa ‘ 4 > StLTrine as neating causes Nné 3 a0 L cE @| sf SUD= ae - + 4 a ce ree 2 " - 4 4 . 72 Poms stances tO separate out in a DULVeEr'’ oS Qihishb= ” eats ae si sti ah : t bl m ‘ cul Ste . ey eee cult to mani ° i os + ,ered separat Or, and the residue in the eaker trested wi 4 cessive portions of acidulate Ger (2cec. uric acid ) ) Fae ‘ ¢ 4 i O € t } 7% ATE C aT 4 a ed ; r ; ee ee LCLOLE Ch a Cig D r-C nd I O «Ce VAavE mals aie : rom »4 > : me a re P ‘ ~ : . 4 | =: } ? “ KUL ACU e- oS aS sa x i EctuuUuat DLOCKE \ ‘ Y . 0 a ee “ a saa cl ! Ul b | i / L Lon ° 4 iS qut! Of Ee wth - > . ‘ " : c ‘ ' ; ¢ : . ‘ t ; ' : : : : } . t ¢ o : 7 Fae by repercolation, ut < SoCo i. requ . 4 4 ' i i , . er I ) Yar ) ra = i > ; . oud al i a ere) eee abate : st 4 ( + Y 4 — ae | + 4 7 _ - ~ 4 t 4 bite Jt 2 Ge LS LILA IaS5 LOT OULD 31] a L L S F ipa (a . i Ul heats aks SS LL wn A +4 i % 6) hn. e NO} t 7 : Gi ; ) to constant al. ] rel . 1% Ne 7 _ 4 ‘ 7 4 a ~ = 4.----Determination of Total Cantharadin:- Twenty -_ ; r 7 « - mrrbhrnD &. an bee ake e = wp P| 4 s4 ao + rtval Lt oO ° y t L -Lat Cc ei teete : = , ve CLAL 16d yi} - mae a ae He ee ee UOLOr oi orm---- -_—-— -— — - -- — <= } } 4 a L. ~~ i it LIK : f ‘ ae. ih cdl Fi ) " ] 4 ~ 4 26 . - | C I Loco... tempo tal Cs ce tn € a a! ] E A 4 a4 < - VL stad | Lwt miAAI » > Lt trac os ~ Vv 4 4 1 f I ; } L ° \ U 30n Tt PLL b seme GLE 4 : ] > ALliLO { ; fis Ppov_e { i 4 ‘ I e] asned with sg Ll au ee the TF CCN MALLET. 1 ‘i f i ° Le . added to the petroleum spirit solution and the mixture warmed until coipletly saponified; during this process most of the petroleun spirit is dissipated. The soap solution thus formed is diluted with warm water and trans- ferred to a separator,sufficient petroleum spirit being added to dissolve the fat acids when liberated; it is now acidified with hydrochloric acid,when the fat acids rapidly rise and dissolve in the petroleum spirit. The aqueous layer is quickly run off from beneath the petro- leum spirit solution, into another separator, the petrolcnn spirit solution washed with water and the washings acded to the first. The cantharadin is. then removed by shaking with successive quantities of chloroform as long as can- tharadin is removed;this,of course,must be ascertained. In the chloroformic solution thus obtuined,the residue from the alcoholic washings of the crystallized canthara- din are dissolved. 236.----The chloroform now contains in solution chiefly cantharadin and the green resinous matter previ- ously mentioned. It is placed in a separator and shaken with lime water, containing excess of calcium hydroxide suspended in it and solution of common salt,the latter causing the chloroformis layer to separate more quickly. In this way,cantharadin passes into aqueous solution probably as cantharidate of calcium,while the chlorofor- a -an mt RT NnANG Co " naa 44 anaA A i 2 ap nese s mis layer containing green resin and coloring matter is . ;a 7 1, an “75 ~ wt+4f ,a PIT + Anas rPrAIAIPfA A rit % Bol > Be 7C L@de The ame LU Te) AS sol AU LOI es) LLUGYECAs, A2CLAL 1ed Wite lahiae L 7 } sholka _-+ ete ray hydrochloric acid and shaken ou r10N cnhirorororm » DCL OL m 0 ie al 7 a “12 1) + 5 ’ , a “ys . _- 1215S CHhLOroLOrM1s Solution 1s added to the cantharadin prev ously soparated, evaporated cautiously, dried in 2 es iccator il weighed. In this ra oerystalline resi- Loo LU00 lf 4.10 2 L219 . i VILLS TAY > VLY@vuaLtLLtLilLg Loot lue of Gantharadin only very slightly colored is obtained 23¢ .---Proportion of Caniharadin in the drugi- as- says by Marvin(oo)show a pereeutage of canthiaradin na ing trom 0.20 to 1.06 percent F.A.Thompson(5?)rsported m1 seven samples containing from a trace to 1.09 per cent;Average all but the worst sample 0.97. per cent. 238 .#FPCinchona Barky#sf----The genus Cinchona is composed of over three dozen species, less than a third of this number furnished the cormercial barks. It is well known that the origins] souree of this drug is South America, the area of the growth of the various - species being confined @c2113 -r3 7 bo Sh? Anies, shiefly on.the eastern side of the Cordilleras--occasionly on the western face, which is covered with forests. The cinchonas séldom form an entire forest, but rather crows interspersed among tree-fernsy gigantic climers, banmboos, etc.,sometines growing seperately in exposed situations, but under peculiar climatic conditions,such as a gr filtrate wi . IntDn can “AY ‘ > liite AAR ANG ners wi iv VY L oo f , vV Ul 9» C ry . ° t 4 w § 5 DS tiga bs ACL an 7 2 fA fn TS . ~ ’ , ycret ‘ansrate the arid ao ©C.C. VALE, ILA : ? irate tie acl1a solution, repeat tne wasn e Eve: = OrtLONS “ a | “ patel OL AS AULated 7 ai Lu at ii ,e ni ‘ - add one cram of sodium an tassium tartrate j \ Se well with 2 x] dd ron 4 OC Ce After hour, collect >. quini: sinchonidine tartrates on a aa Fs Of. cht ’ rera] small portions of ter L ress, t _ PRS weigh multiplied by 0.8 \ Pa te Bat * Theo nine and cinchonidi B.e.-) Bae inder of 1 alka- loids is contain in iLltrate and washings: wi solution of yon. é { 3 SS. Colle the preci } yunternpc ( ] rs oress dry and ag L , ff the* quini and Ginchonidine already ovtain¢« i that of total ale kaloids in 15 gran a lrug. Of course, tne precipita- tion with ‘fetes avid. pot lun tartrade A omitted if we desire only total alka loids. ( 7 " > —e = mA ‘ is Rie oe a) 248. Me of U. S. Pharmacopoeiat- To 20 grams of cinchona ~ a very fine ,. and contained in a bottle f ted with accurately ground stopper, add 200 c.c. of a prev ly prepared mixture of 19 volumes of alc ohol , 6 volumes of chloroform and 1 volume of ammonia, stopper the bottle and Shake thorouz and fre peperend during 4 hours, Then pour off through mel .cont ainir pellet of absorbent cot- ton, 100 c.c. of the solutio: j eee senting 10 grams of the bark), and evaporate to dryness. Dissolve the residue in 10 ¢.¢. water and 4 c.c. normal sulphuric acid with the aid ad 5 “ant ~ + . my | 4 4 - 4 Wayrat ars 2 7 wna Gi. a gentle OeAaAL, COOL, Au CL 2b) eperatorys UNINeL ana wash breaker and filter unti. she filtrate is no using the smallest prect Le —1NuT ' water, BAG CGeGe OF - o rAtac . a , : . ee } = iy Pee } ye normal potvassl1u nyarate to rendey eciacead oJ LLINe ana ese tract alkaloi wakes ‘-e first wit a0 cece. and then repeatedly wit POS olofor nit rov of the ~ =" > : Last ChLoroir or Cc. : f rit I € i Cc Iorated on > watoeh 7 Wrxraf{y)y ; toa pay Jeglrear > at 7 a0"? da VAUULL (4 AND e Pi 4, J , wd : , i ae \ UW) We and weigh. 249, ie practical difficulty in the above process is dered bark are mixed wit 5 grams .- me and 75 graas of a solution of soda 40 two alkalies is essential ior t Bo alkaloids. Two litres of pet! e mixture heated at 100° C. for 20 i { agitation. lie pet ecan treated in a similar way wit ecol . ~ 4 ~~ Y é litres of oil are then agitated for 10 LAGres OC aed aS & > = a 7 : . lan = or a. SULDOUr LG aC R I ‘ U e oY decanted off and tue 1 9 third time with 1/2 th Oy 2 : } ) } Bs + i o LEDOs it EY t IY pa ‘ = = - : eS » t r adopt ed Tor 4~ne assay O Which was genei lL: 4 4 ee Pe ey ee Loa 2anotvanlic LOS & jon 6f lime: For tinis reaso fallen into disuse, pi : ‘he process was as I : lime are mixed 5 ( eu dl r, 20 strong ! acid reaction a 19 filtered to separa Lu by distillatioi ym 1 " ] Lr Cw \ vs a { of ¥ | i ‘ acerate for — erosese 2s Nyy xa nr proeess O ely pow- oo Sie ; W y Ler Baume. The use of LOUE 117 Lr as ~ > , ove 7 < UC > i 3 7 es ) ~ ay Fs oa oe - \ lpg ati oT a NY ob Aa : 7 oO \? x Tale ala rPR mB aa A = re 1TaQAUE ro? . as > 253. Assay for total alkaloids (63) :- 20 grams of very fine powder are placed in a flask holding 500 c.c. of 10% ammonia and 20 c.c. alcohol of 94% added, and a mix- ture well shaken. Then, 170 c.c. ether added and shake occasionally for 2 or 3 hours. Then decant 100 c.c. of the clear liquid into a separatory funnel containing 5O csc. water and 2 c.c. dilute sulphuric acid (sp. er. 1.117), or sufficient quantity to give the aqueous solu- tion an acid reaction after agitation with the ethereal solvent. Separate the yellowish acid solution from the ethereal layer, warm to expel the dissolved ether and return to a clean separatory funnel; add 300 c.c. chioro- form and then enough ammonia to precipitate the alkaloids and agitate at once for several minutes; the chloroform sOlution is received in a small tared flask and the agita- tion repeated with portions of 20 c.c. each, until the alkaline solution after acidifying, fails to give a pre- Cipitate with iodine solution; distill off the chloroforr or allow it to evaporate, dry contents at 100°C. and weigh. In case the chloroform forms an emulsion when shak- en: with the alkaline solution, it should be poured upon @ filter well wetted with chloroform, stirred with a glass rod and washed with a little more chloroform. The success of the method depends upon the fineness of the powder used, 254, Schwickerath Method (64) :- 3 grams of the drug, finely powdered and dried are macerated with 150 c.c. weak Prollins mixture for about 20 hours, shaking frequent- ly (it is best to use an agitating apparatus). Then fil- ter off 50 c.c. corresponding to 1 gram drug. Place ina shallow dish, add 10 c.c. dilute hydrochloric acid (1 to 10), and evaporate the alcohol and ether at moderate heat, The acid solution thus obtained is now filtered into a perforator and method conducted as per (51). 255.4 Assay by acid was also formerly much used. The method of Dr, De Vrij gives fairly good results and de- pends chiefly upon the facts that the alkaloids are dis- solved out by means of a mixture consisting of 88 parts ether, 4 parts ammonia and 8’ parts alcohol, After macer- ation and separation, the solution is evaporated to dry- ness, leaving the crude alkaloids, which are purified by solution in acidulated water, filtration and precipitation by means of an alkali and re-dissolved in chloroform which upon evaporation, leaves pure alkaloids, This process has been improved and made a very easy method of assay as fol- lows:- 400 grams of the bark in fine powder are boiled for 10 minutes with 5 ounces of water and 45 minims strong hydrochloric acid. When cool, the liquid portion is fil- tered through absorbent cotton placed in the neck of the funnel, into which the powder having been transferred, is rather tightly pressed and 2 ounces of water poured on and allowed to percolate, This is added to the filtrate and the powdered cinchona again boiled with 5 ounces water and 50 minims acid. This is then filtered same as before, using same funnel and cotton. The bark is then thoroughly exhausted by percolation with acidulated water, the acid being used in proportion of 5 minims to fluid ounce and requires in all about 5 ounces, The filtrateés»are now my re a Ca 2 mixed and re-filtered through absorbent cotton. The fil- trate is then thoroughly agitated with 6 drachms chloro- form and after clean separation, drawn off, The washing is then continued a second time with like amount of chlo- roform, 256. From the acid solution above, the alkaloids may be separated (a) by precipitating with caustic soda in excess, (add to weight obtained, as a correction for solubility of alkaloid, 0.000585 em, for each c.c. of filtrate and washings) or (b) by adding excess of caustic soda and shaking out with chloroform. Evaporating, drying and weighing. The author lays particular stress on the avoidance of heat in the extraction of bark with dilute acid, and declares that sulphurie acid will not completely exhaust the drug while hydrochloric acid certainly will. 257, Modified Assay Process:- Ekross (66) proposes the following process, which is a modification of that of C. ©. Keller, 12 grams of the finely powdered bark are macerated with occasional agitation, in a mixture of 120 gm ether and 10 csc. of a 10 percent. solution of sodium hydrate, during 3 hours and 10 c.c. water are then added to the mixture; 100 gm of the clear ethereal solution are then weighed direct into a separatory funnel, shaken with 50 CeCe w/10 sulphuric acid, the ether washed twice suc- cessively with two portions of 20 cece. water and the united acid aqueous liquor is titrated with w/10 potassium hydrate to determine excess of acid, haematoxylin being used as indicator. l'c.c. W/10 sulphuric acid corresponds to 0.034 gme alkaloid. 298, Assay with the aid of Chloral Hydrate (67) :- The extraordinary solvent action of a concentrated solu- tion of chloral hydrate (8 to 5 parts of water) upon the dry cell contents, well known to microscopists, has been successfully applied by Dr. W. Lenz, to the extraction of alkaloids in assay processes, but more particularly to the assay of cinchona bark. By its use, the troublesome pul- verization to extremely fine powder as well as the appli- cation of strong reagents, is avoided; the process as given by the author is briefly, as follows:- 10 grams of the powdered bark are moistened in a flask of about 300 CeCe. Capacity, with a solution of 20 grams of chloral hy- drate in 12.5 grams of water, and allowed to stand over night. The somewhat tough mass formed is heated for 1/2 hour on a water bath with 150 csc. dilute alcohol and 2 gm, of hydrochloric acid, filtered through glass wool and the residue washed with the aid of a suction pump to complete exhaustion with warm dilute alcohol, containing a few drops of hydrochloric acid. The alcoholic solution is concentrated to consistence of syrup and this is then carefully mixed with water acidulated with a few drops of hydrochloric acid, so long as the separation of resin takes place, observing that this separation of resin shall be flocculent and not in a coherent mass, The filtered aque- our solution is then made alkaline with soda solution and the alkaloids shaken out with three portions of 100 CeCe, SO and 50 c.c. of chloroform. This chloroform solution of the alkaloid is then, in turn, shaken out with three re “ rt a re oO, portions of 100, 50 and 50 c.c. water containing 2 percent. hydrochloric acid and finally with small amount of pure water, The acid aqueous solution is then again made alka- line with soda solution and shaken with 100 c.c,. ether, the ether solution removed as soon as it separates and this shaking out repeated in the same manner, using fresh portions of 50 c.c,. ether, until nothing more is exhausted by that solvent, This part of the process must be carried out with oapertness and expedition so that the alkaloids which are with difficulty soluble in ether may not sepa- rate from the solution into which they have temporarily entered, Evaporation to dryness and constant weight at 100°C. finishes the process. The alkaloidal residues ob- tained in this manner, are colorless and apparently purer than those obtained in most assays. 259. Acetic Assay process of Dr, E,. R. Squibb (68) Ten grammes of the powdered cinchona in a capacious cap- sule is moistened with 10 c.c. of 10% acetic acid, the lumps all well broken up, the moist powder packed firmly in some form of yeseeiacer and percolated to complete exhaustion with 10% acetic acid, Tne degree of exhaustion is judged by tne degree of bitterness of the final perco- late which is not quite bitter free when the lower part of the powder is quite bitter free though not tasteless. er Sala > ®o = 4 a ; — OM 47 ant ays An = eS jd 6p O | ci ‘> —~! ‘y AY i 1 F f Y G& UQ f ' ¢ ; . “oe - ae | Ls ! i ' 7 a p> co i Co >) , = i 2 + apeoee { » 7 ¢ r cf - 2 ‘ eS a ~ F ’ q | x ie > & TT 42 4} ; os op . , B. SS ad = ) D¢ ri ~ ue ( > Oo : > ¢ ; rd $3 4 ; C im - t =. e bd oe | Pa ‘ > r g 2 ; cs f : . re ( t i> > } mt oT oe 4 a ’ t + "s / a ‘ 1 rf ° a . a) 1° ' r-| r 5 45 ay 4: * “) - L ‘ Pe o ; 15 &., C _ i © f f ~ % \ aay 7 y . : — r c eet } . @ er } ro X c _ , = i - s i = ' . Ey «€ * C5 ord n | c : . 5 ie 1) © ; . 4 } 0 : oO ® ¢ o : 2) \ 4 * * ~ 4 A ? a rae C4 = a + 4 W e 1 ™ > ; ~ - ‘ = “ys | 5 ih — cenen : ~¢ a : ° ‘ a VW i i? {I OM oe 4 as i af | f = i> H > dp) 4 U a ac @ 49 ory ~ + chioro ‘ 4] 2 c m4 pe r ® * t S es 4 f . mi = he — > oO 1 ‘> 2 ¢ » _| WY oO 1¢8 a a mon Oo 2 TC ci > xa ; ¢ t £ e: @ co - © : ri To oC 5 rm + » a er] ort ] - 5 4 ~ j 4 a3 4 ¢ mad : ” aed — fe ) + \ dD @ C - ie L a er » : Sy © > a ) 7 e al re rat f 5 > as ¢ 4 | 5 , a+ r Te ‘ ’ xm) 4 , oo | 4 rier ~ 25 j - nN 1 / 5 - ‘ L oi my Sy Od 4 in 5 —t a4 ‘> i 4 r . ‘ . | a ae by id ™ OD r- ew . €& rn 1 ey ' = : r © rr) > } 2) os : = om)» e q oO 5 ud ‘ ire = »o ¢ aah, “4 . ’ ' WY r ‘ WV + ; + ‘ a j | j + ol 2 WA 4 r 3 ey + ¢) ~~ aa re adit fails to for five liquid is solution at . the emulsion separator, allowed to this washing t 264. The watery portion is now tested and should be found bitter free, or to be againether-~washed The ether solutions in the tared beaker are boiled oft in the bath and leave a varnish like residue of an ambe color, consisting of total alkaloids and a little in- soluble waxy matter. This is weighed in order to the approximate percentage of alkaloids, and for each one percent of these crude alkaloids, 5 c.c. decinor- mal acid is rum into the beaker from a burette and 10 C.C. Water added. But these alkaloids are difficult and slow to dissolve in the acid, so that time is sa- ved by first dissolving them in 3 or 4 c.c. ether, by rotary agitation, before the acid is run in. When the acid is run in, the waxy and fatty matters are precip itated and a stirrer and / sapling 3 are then used to freé this precipitated matter from kaloids and to drive off the ether. The Alkaloids are thus converted into acid salts and dissolved and the insolubbe matter is deposited on the sdies and bottom of the beaker. it the nearly clear solution be now evaporated and the weight taken from the weight of crude alkaloids, the pure alkaloids are known. The alkaloids may then be precipated and dissolved by eat paleae solvents or tetrated. 265. Assay of the alkaloids of Cinchona Bark:- As a general rule, it is sufficient generally to determine the amount of quinine in a given sample of total alka- loids and the most simple wey is first to convert the mixed alkaloids into sulphates. Dilute the solution moderately, heat to about 85 degrees C., neutralize carefully and cool, when the quinine. sulphate nearly all crystallizes out, accompanied by a small quentity of the other alkaloids. Another plan is to precipitate together quinine and cinchonidine as tartrates, as in tge method of the British Pharmacopoeia (247). In the case of red barks, rich in cinchomine, this is not very satisfactory. A third plan is to determine simply the total ether-soluble alkaloids (practically quinine and cinchonidine), or better the amount of alkaloid, which is held in solution one hour by a limited amowjt of ether, cinchonidine, which is taken up freely when first precipitated, being soon deposited in crystals. 266. The method of the U. Se Pharmacopoeia is an attempt to come still closer to the quanity of quinine. It is conducted as follows:-- The alkaloids from 5 grams cinchona bark, by whatever process it may have peen extracted, is brought into solution in chloroform (or alcohol) andpoured little by little, over about 5 grams of powdered glass contained in a porcelain cap- sule on the water bath, causing the powder tp absorb nearly all of the alkaloid. The solvent is wholly driven off, the capsule allowed to cool and the powder moistened with ether transferred without loss by aid of successive small additions of ether to an evher moistened filter ? om in diameter, in which it is treated with ether, drop by drop until exactly 1@ CeCe of filtrate are obtained. The receiver is then ch langed and the treatment with ether continued until another 10 e.c. has been obtained. 2967. Evaporate in separate tared capsules, the two portions of ether, dry at constant weight at 100 degrees C. and weigh. fhe resid@e from the first por- tion will contain nearly all the quinine together with m4 a portion ofthe less soluble alkaloids. The secon portion will contain about as much of the less soluble alkaloids as the first, with almost no quinine. We have then simply to deduct the weigt of the latter from that of the first to obtain the amount of quinine in 5 grams of the bark.The method is faulty, in taking no account of amorphous ether-soluble alkaloids of Which there may be a notable quantity present, reckoned by th&®s method as quinine. The alkaloidal residue dried at 100 degrees Ce, will cont ain still one molecule of waters; to convert into nant ob alkaloid, multiply by 0.947. 268. Another mode of determining ether-soluble alkaloids is that of Dr. Otto Kaspar. Dissov¢e the 3] ~ kaloids from 10 grams of the bark in a slight excess of hydrochloric acid, make up to a volume of 10 c.ce, add caustic soda in excess (according to the author, 15 grams of a 10% solution) and shake irmediately with 15 ec. ethers separate the ether and shake again twice with fresh portions of 15 cece each, unite the ethereal solutions, let stand at least twelve hours for the crystallization of the less soluble quinidine md cinchonidine, evaporate, dry at 100 degrees C. and. weigh. It seems that the quantity of ether a5 well as that of the soda solution, is needlessly larger than is nevessary.e. With a moderate excess of soda solution and three portions of ether, 15, 10, and 10 c.ce, the results would be as wells also, it seems as though better results would be obtainéd in the use of petro leum-ether in place gf ether, but experimentation would be necessary to determing the quantity of thia solvent required. Perhaps a still better plan would be to extract the bark direct with petroleum-ether and ammonia, let stand 24 hours for the crystalligation of the less soluble alkaloids, and recover the alkaloid in pure form by shaking out with acidulated water, reder- 2 ing alkaline and shaking out with ether. 269. Method of DéVrij, by precipitation with Chin- Oidine iodosulphate. (69):-- Dissolve the mixed alka- loids in 40 times their weight of 92% alcohol, contain- ing 0.76 percent of sulphuric acid (or dissolve in normal sulphuric acid, using 6.2 c.c. for each gram of alkaloid. Hvaporate to one-half and add 46 c.c. strong alcohol for each gram of alkaloid). If the bark under examination contains a large porportion of cinchonidine, @igest the crude alkaloid in powder with 10 times its weight of ether; after standing half an hour or more decant the ether and wash the residue with a small ad- ditional portion of the solvent. lvaporate the dryness, the etherealsolution, which will contain all the qui- nine and employ this instead of the total alkaloids for the test. 270. To the solution in sulphuric acid and alco- hol, add solution of chinoidine iodosulphate (27) from a pipette, drop by drop, oMrrtag constantly, as long as @ dark »rownish red precipitate of herepathite is Produced. As soon as ,all the quinine is precipitated and a slight excess of reagent added, the solution ac quiresan intense yelldéw color. The beaker is now to be covered and heated to boiling on the water bath. Cool, note the volume of fluid, filter and wash the previpi- tate on the filter with a saturated solution of here- pathite in alcohol of 9%. Dry the precipitate at 100 degrees C. and weigh. Add to the weight found, for ach cece Of fluid previous to filtration, 0.0011 gm., as a correction of solubility of the herepathite in al- cohol. Multiply the corrected result by D.55055 to ob-~ tain anhydrous quinine, or by 0.7409, to obtain crys- tallized sulphate of quinine. > 2°71. Improved Ether method of A. Petit. (70):- Dissolve the alkaloids from 80 grams of cinchona bark in a slight excess of sulphuric acid, add 25 o.ce ether and 5 @.ce water of ammonia and shake. Decant the ether into a vial, shake the alkaline solution once more with 10 c.ce ether, which is to be added to the first ethereal portion. Let the ether stand 15 min~ utes. Decant the clear solution into a separator, add 10 e.ce Of dilute sulphuric acid (1 to ®), shake and separate. Wash the @ther a second time with 5 cice of the same acid, and then with water enough © make in all 25 cece of fluid. Heat this in a beaker to boil- ing add cautiously dilute solution of ammonia until the liquid is faintly alkaline, coob to erystallize quinine sulphate, which is collected on a tared filter, washed with a saturated aqueous solution of quinine sulphate, dried at 115 degrees Ce to constant weight and weighed as anhydrous sulphate. 272. Oxalate Method of G. Shimoyama (71) $-~ Dissolve the alkaloids (at least 0.5 gm.) in a beaker in 80 or 40 cece Of water, by aid of the smallest pos- sible amount of acetic acid. Filter into a tared beak- er, wash the filter and neutralize exactly with dilute solution of soda, add for each gram of the alkaloids, 10 e.ce of a cold saturated solution of sodium oxalate. Concentrate on the water bath, to 8 or 10 grams ,should a slimy mass separate during the concentration, it must be filtered off and well washed with boiling water. To the contents of the beaker, add 10 to 15 c.c. of water and stir until a clear solution results. Set aside three hours at a temperature af 18 degrees C., stirring frequently. Collect the precipitate on a double filter and wash thoroughly with a saturated solutionnof qui- nine oxalate. Dry at 110 degrees C., weigh and add for each cec. of fluid previous to tetration, 0.00064 gm. to obtain the weight of the quinine as oxalate. Mul~ tiply this by 0.873 for anhydrous quinine, or by 1.13919 for crystallized quinine sulphate. by 58! —) ©2783. Full Assay of Cinchona Alkaloids. John Muter (72) directs to dissolve the alkaloids, which have been weighed after drying at 116 degrees Ce, in absolute al- cohol and divide into two equal portions Ae and Be To portion As, add from a burette, wolumetric sulphuric acid (11.6 grams of acid sp. gi 1.848, to one litre of water: each cece equals 0.1 gram erystallized quinine sulphate} wntil just faintly acid to delictae litmus paper.and note the quantity of acid used as a guide in p the further operations. Evaporate the 2leohol and dis- ) solve residue in water at 85 degrees C., using D CeCe a water for each cc. of volumetric acid used. If nec- essary, add a little of the volumetric acid to effect complete solution. Keeping the temperature at about 85 degrees C., add cautiously, drop by drop, decinormal s@lution of caustic soda until all but neutral. 974. Cool,the solution rapidly to od pt Cos keep at that temperature for an hour, fil through a pair of counterpoised filters, and wash "ton crystals with a little cold water (1.5 c.c. for each coc. of the volumetric acid used in the preliminary titration). Drain the crystals, press, dry at 109 degrees C., rais- ing the temperature gradually to 116 degrees C. and weigh as anhydrous quinine sulphate. (In the wegen eng: bear in mind that this is exceedl ngly hygroscopic it should be weighed in a weighing b ttle, securely ae pered). Measure the filtrate and wash ings, and for eact e@.ce of the fluid, add to the weight actually obtained, 0.000817 gm, as a correction for the solubility of quinine sulphate in water. Multiply by 0.3686 for qui- nine alkaloid. 275, To portion B. add hydrochloric acid (dilute), until it has a faint acid reaction, evapor&te, and dis- solve the residue in 2 minimum quantity of water at 38 degrees C. Neutralize accurately with decinormal soda solution, add a saturated solution of sodium and potassium tartrate in excess, cool and keep at tempers- ture of 15 degrees C., for one hour, frequently stir. ring. Collect on a paid of mutaally counterpoised fil- ters, wash with 100 cece of water at 15 degrees C., dry at 104.4 degrees Ce, and weigh. Add for each CeCe of filtrate and washings, 0.00083 gm. to obtain weight tartrates of quinine and cinchonidine. Deduct the we of quinine tartrate, found by multiplying the weight of anhydrous quinine sulphate by 0.915. The remainder, multiplied by 0.804, will give cinchonidine alkaloid. 2-6. Concentrate the filtrate and washingesfrom the tartrate to its original volums, ae. render faintly acid with acetic acid, and add with constant stirring, an excess of a neutral aaturated solution of ites atu iodide. After an hour or so, collect, wash, dry and weight precisely as in the case of the tartrate. Add 0.00077 om. for each C.C. of filtrate and washings and multiply by 0.71 or quinine alka- loid. hb C2 277. From the filtrate and washings, précipitate the rest of the alkaloid with sodium hydrate, colle ct On a pair of mutually counterpoised filters, wash, dry at 104 desrees C. and weig gh. Heat with 40 percent alcohol to dissolve out amorphous alkaloid, dry the residue at 105 degrees C. and weigh as cinchonine alka- loid. The frerence between this weighing and the previous one gives the quanity of amorphous alkaloid, but must be cyrrected by deducting for each ac of filtrate from the precipitated tartrates 0.00066 ogn., and for each cece Og filtrate from quinidine hydriodide 0.90052 om e i 0 di 2°78. Assay the Galenical Preparations of Cinchomea Bark:-- For fluid extracts:-- put into a 25 c.c. meas- uring flask 5 cece of the fluid extract and fill to the mark, with dilute alcohol. Use 5 c.ce of the mix- ture equivalent to 1 gram of the drug, fr the assay. £f the fluid As thought to be poor in alkaloid, use 10 eece instéad of 5 c.ce tO make the dilution. Assay according to detail in (150) to (152). Should there be any tendency to emulsionize, use Thompson's saw- dust process (159), 2°79. Carl Schwickerath (73) di to put into a 50 c.c. measuring flask 10 c.ce of te Hydrochlor- ic acid (10 percent), add 5 c.c. of the fluid extract (with Cinchona Comp., 10 c.ce), shake, make up to 50 CeCey Shake well, allow to settle and filter. Put into a perforater (9), 10 c.c. of the filtrate and extract one hour with petreleum-ether to remove fatty substances then add an excess of caustic soda and extract 8 to 4 hours with a mixture of chloroform and petroleum-ether Pour off the supernatent liquid into the flask md evaporate the solution on a steam bath preferably with the aid of an air current. The alkaloids thus dbtain- ed are perfectly wiite. Dry for a short time at 100 degrees C. when they will become slightly yellow. Fi- nally determine the amount of alkaloids by weighting. fhe weight obtained xl00 (with cinchona comp. 50) -per- cent alkaloids. 230. Solid Extracts are to be treated on the gen- eral principles stated in (171) et. seq. 231. Proportion of alkaloid present in Cinchon Bark. The U. S. P. requires that a bark shall contain So percent of total alkaloids and not less than 21/2 percent of quinine. The barks offered in » Se URE et vary from 4 to 7? percent, the average running from about 4.4 to 6 percent for yellow bark; and from 4.5 to 8 for red bark. The richest government bark brought to the market, until recently, has not exceeded 9 1/2 percent of sulphate of quinine; 7? to 8 percent is a good average in government plantations. Bark from the trees in the government gardens at Pioeng Goenoeg, Java have been recently analyzed and found to equal respe@- tively 12.66 and 16.04 percent of quinine sulphate. >) O Barks however, of this nature are not upon the market for sale. The standard of 5% for total alkaloids is a p EAS & good average of commercial barks. COCA LEAVES. 282. The leaves of Erythroxylon Coca are obviate or lanceolate, entire, from 20 to 70 mm. (4/5 to 2 4/5 in. long; midrib prominent, with two distinct curved lines at equal distances on each side running from base to a- pex; these lines are not ribs, howeve r, but are folds caused by the manner in which the leaves were rolled in the bud; dark green on upper side, lighter beneath; odor Yr. tea-like; taste bitter and somewhat aromatic tempo re ily b] = : z d £ v benumbing the lips and tongue when chewed. The leaves cul- utl tivated in Java and India are inferior to the Sou Ame rican variety. 283. The chief constituent of the leaves is the alkaloid cocaine. It is seluble in ether, petroleum-ether, and kerosene oil, by means of which solvents, it may be completely removed from alkaline solutions. The alkaloid is represented to be a methyl benzoyl compound of another Organic base, ecgonine. This complex body cocaine is readily decomposed into its component parts, methyl a cohol, benzoic acid and ecgonine, by heating with hydrochloric acid. Hyd rochlo ric acid, therefore, is un- Suitable for the extraction of cocaine in the process cf manufacture. Hence, being an unstable body, we must avoid heat or prolonged contact with st rong alkalies and acids. 284, The assay may be made by the short assay process No. 3, (75), which yields a particularly pure alkaloid. The main object in coca wert is avoidance of heat, strong acids or strong alkalies for any length of time. 285. Schwicke rath hel pare Digest in an agi- tator for 12 hours, 12 grams coca-leaves, with 95 c.C. benzene, 1 c.c. 30% ammonia and Na c.c. alcohol. Shake vigorously and then let settle; filter through cotton 50 c.c. (equivalent to 6 grams of the drug) add 2 c.c. dilute sulphuric acid (BI52):, and & c.c. water, evaporate alco- hol and benzene, and filter the acid solution into the pe rforetor. Wask first for one hour with ether and after adding 4 or 5 c.c. dilute ammonia, extract 3 or 4 hours with ether. Evaporate ether and determine alkaloid wi n/ 100 sulphuric acid. 1 c.c. acid - .00303 grams alkalo 0.2 by oa K Ror ~~ mF ~ 5 i lea t+ AWN my +) Amm > 7-") 286. Assay by Percolation with Ammoniated ether:- oh = - As Gurr “* ' prefers pe reolation to maceration and pro- ceeds as follows:- Moisten 5 grams of the vowde re<¢ L : + +1, 4 ere leaves with a 2% solution of ammonia. After half an hour io \ place in a narrow tubular percolator (25x 1.5 em.) and percolate with ammoniated ether to obtain 1 : From the percolate, the alkaloid is washed out with 5 . portions of 2% hydrochloric acid, in all about 50 ¢.c. from which in ti im, it is finally extracted with ether after addition of ammonia. AaAn ‘ 2 a 33,3 (76) 7 = 237. Kefosene process of Dr. Squibd* ;- LOO grams of the powsde red le: aves are moistened with 100 c.ec. of a ei ot solution of erystallixzed sodium carbonate, packed at once in a percolat ‘or and percolated to about water mitts kerosene. The percolate is shal successively with 30 c.c. of water contain hydrochloric acid. The acid solution is we 50 c.c. of ether to remove fatty substances, Solution being rejected? Then 20 c.c. of etl with 10 c.c. of a solution of sodium ci n 24" grams of the crystallized Squibb dirécsts to use sodium neutralize the acid taken , an there must be a distinet but fluids well shaken toget escaped he ether 15: 5e}] d twice with 20 c.c. of fre are transferred to a tare weignt, the weignt of th cent of alkaloid. 238. The above procedure recommends itself by its directness and cheapness vate furthermore, it gives us a quant Mey of alkaloid sufficient to use for further deter- mination of true cocaine. “This may be carried out accordi- ing to Grandval and Lajoux, by adding water equal to ten times the weight of alkaloids, and just enough hydro- promic acid to neutralize co: npletely, heating the solution on the water bath and saturating rapidly with potassium bromide. On cooling, we obtain a crystalline mass of the double bromide of potass Sium and cocaine. Percolate the erystals in a funnel having the tube rather fimly plugged with absorbent cotton, with a saturated solution of potassium bromide, which will re move ecgonine. Finally, dissolve the erystals in hot water, cool and treat with ammonia and ether to remove the pure cocaine. 289. Koehler’ ’ ‘inixes 50 grams of finely powdered leaves with 5 grams of dry crystallized carbonate of Sodium and 15 grams of oxide of lead, macerates with 50 Cec. water and dries in vacuum at a temperature of the water bath. The mass is then twice macerated for 24 hours with 250 c.c. benzin each time, the alkaloid wi ids, wn from the benzin with hydrochloric acid which in tum is treated with sodium carbonate in excess and bate out with ether. Van der Marck‘ 3) maxce 8 50 grams of the powde r- ed leaves with 20 grams of magnesia, dries at 60°C. and extracts with ether, The solvent is distilled over, the residue taken up with hydrochloric acid, 5 A the acid solution treated with ether to remove coloring matter -~ Vlee we ASAE, Ati Ser Seelin 4 ee ehatlar awt ete @9 made alkal ine Wii Url aim 1Oy 1 1a Wa t c Y, and sna en Ou with three suc cessive portions of ether (25 C.C.). Alex a : ~ Po) See es +1, 7+ ander Gunn‘ '’/ reviewing the al fferent methods, decides that Lyons Ammoniated ether process is the best method, the only objection to the process peing the time, it re- quiring 24 hours to complete, though there is no doubt that the extraction of alkal oids is complete. As a result his work, he has modified the operation so that it maz pe completed in about two hours, as follows:- 5 grams of the powdered leaves are dampened with (2 solution of about 2% ammonia and allowed to stand for 1/2 hour. Then, placec in a narrow tubular percolator and percolated with am moniated ether until 100 c.c . are collected. This i shaken out with 3 washings of 2 per cent hyd rocht acid, collecting about 50 ¢c.c. in all of the ni This "acid solution is then washed once with ler made alkaline by ammonia and shaken out with 3 successive portions of ether. The ethereal solutions are careful Ly transferred to.a tared dish, evaporated and weighed, afte drying at 75°C. 290. Galencial Preparations:- Fora fluid ext rac, follow the routine of (150) or (154), using for the first extraction ether in place of ether and chlo roform; as an ae Vv alterative, the saw-dust process (169). Tine’ be and wine may he evaporated at very low temperature and treated (159). Solid extracts are treated on general seine Jles yi71). Yhen saw-dust is used, the solvent may be ether or petroheum-ether, as in the assay of leaves. 291. Proportion of Alkaloid in Coca leaves:- Coca leaves of good quality should yield of total alkaloid, as much as 0.6 per cent. Out of 15 samples examined, I have found the following percentages:- .63- .52- 9=- .69= 06 58- 61l- oD = 62> -08- ~67- 435= 48- o- 59 and 6, average .59. The standard strength now employed by lead- ing manufacturers, is 5 per cent alkaloid, this represent- ing an ave rage sample of the drug. COLCHIUM. 292. Two parts of Colchium autumnale are used, namel the corm and the seed. Thev’are described as follows:- (a) An ovoid com about 25 to 40 mm. (1 to 1 3/5 in.) long, flattened and deeply grooved on one side; when dried and deprived of its outer membrabous covering it is wrinkled and of a brownish gray color; intermally whitis: It often comes into market in transverse starchy slices having a: reniform outline, due to the lateral groove; in odorous; taste sweetish, bitter, and somewhat acrid. A very deep or large notch in the slices indicates that the = corm has Springs from the base. g as e 4 G2 ry eZ A vB 2 ~ ~~ — few a ee o & a — —! hy a @ ee rer, 2 a "5 f fs ~ ct — ™ eas jj me + = =~ ular, 3 mm. (1/8 in.) diamet: hilum and with a slight proje ie ps testa thin, somewhat Ae the iife albumen which fills the a Bee aie rized hy its ext reme ha rdne: nearly opposite the hilwn; inodorcus; and somewhat acrid. eo 1) alkaloids in moved from a It is quite ct loroiorm; ym hoo og! wo tated from Mayer's Rea utions. The alkaloid ed, its aqueous soluti i quite neutral. Minera it on application of mind in devising a@ proecés 294, A ve ry good good results is the following method of Place 19 grams of lek powdered drug in edd 190 c.c. of Prollirns mixture modifie urely and mace ya with occasional shaki or place in a mechanical shaker for 4 clear. liquid, pvaneret e in Y Ss . mess. Take ut ] cise hydrochioric or sulphuric and stir until the ether evaporates. Filter he acid solution into a separatory funnel, retaining the nscluble residue as much as possible, in the beak ich it is indeed mostly adherent. Re-dissolve the resi- due in a little ether, add 2 c.c. of the dilute acid, stir as before, and filter the acid agueous solution into the Bohs AbOrs. wash the filter with a little of the acid, adding the washings to the contents of the separator. 295 Je Put jwe nto the separator, 15 c.c. chloroform Shake carefully but econtinuously---a rotary moticn i best---during two minutes, let separate and draw off the chloroform into a tared beake r. Repeat the treatment with two portions of 10 c.c. each of fresh chloroform Test a drop of the aqueous solution remaining after chlorofon has evaporated, with Mayer's reagent; if this shows prezence of alkaloid, repeat the treatment with chlore- form, after having rendered the solution on ele neut ral with ammonia. Three washings, however, will generally ex- tract the alkaloid even in the presen acid. Finall;, evaporate the chloroformic solu es re-dissolve in a little dilute alcohol an to constant weight. The residue is nearly 1 tee! may have retained still some chloroform % should be dissolved once more in dilute ar Ge= ‘ wi . : f iD Vt a volume of 10 c.c. for eolehium yoot or 15 c.c. fo colchiun seed tee dilute huric acid 2. and Mayer's reagent is as long as it preduce > y, < — re Pat = cloud in = loia indi 13 by the fo quantity each c.c. of tien; 0. “ag c.c. Hach c.c. of the remainder w 6 pond with 14.7 milligrams of colchicine. Example- Taken 10 c.c. of acid solution; added 5.4 c.c. Mayer's reagent. 5.4 - 15.4 x 0,08 = 5.4-1.23 ~ AY? then *4 St7 ox WA.) =6L.05 Me. 297. It is better to make = tion as above (295), dissolve th times or dilute sulvl and +i ove. The result ! , when the above arbitrary rule is adopted, will be close if the alkaloidai solution has approximately an initial strengtl of 1.300; if weaker, the results are liable to be too high, Rf " st ronger, low. It is essential that the solution titrated contain not less than of of sulphuric acid; a little more will not materially affect the result. 298. K. ageere Ke rath (80)modifies sl ightly the pro- cess of Lyons, pb: ing a modified Prollins mixture co! taining about 15 c.c. alcohol and 5 ec.c. Stronger wat ammonia instead of 25 and 10 cece respectively. His pro cess as given is as follows:- 20 grams of the drug rather finely powde red are consigned to agitation for 12 hours, with 120 c.ec. of the modified Prollins mixtur Pe rmit fi & C to deposit and s L _ a ttle and then filters off 60 c. (equivalent to € € O grams drug), adds 8 c.c. wat ly acetic acid slow until an acid reaction is obtained, ™h i | 7) , mt - e _* 3 = J alcohol and ether are then evaporeted at a moderate heat J 4 and the acid selution filtered ah rOugS cotton into the perforator. Then, wash the solution with ether for on nour to remove impurities, then add carboniate of sodium to alkaline reaction and extract with a mixture of ether 5 volumes and chloreform one volume, taking care to insert just below the opening of the delivery tube > & ring of absorbent cotton. The alkaloid is to be dried with the precautions in (295) and weighed. 299. Proportion of Alkaloid in ag plehicum seed yields 0.5 to 1.9 per cent of colchicine, about 0.7 per cent. Colchicum root i ul in alkaloid. but a drug of prime qi . 3 = Qt v Lov 0.5 or exceeds 0.75 ave rage EHou t 0.5 ver cent. The e Nag t a 1Za + ion ont + I stan a ra 1Zati10YM1 O21 S VE 7 1+ Pe ye »n Loni Y wry f) 7 “e 5 pe Yr cent 1O0Y colLcniws OO & is Jy regular standard now adop galendcal aes ee ions @ and 0.5 per cent for t 300. Assay of Galenical Preparat extract (5c.c.) the alkaloid can be ing an equal eae of water and shaki chloroform, using several portions of Determine leid exactly as in of, (294). 3; an alternative dil ext ract c. water, add tate in ess (i.e. unti tinctly aste) make up f spall Le Ye 1a yall t race ad a S oa i sufficic hrow down the exc FO a Ss@€parator chloroform, used. a -s may be dissolved in dilute alcchol and et treated as fluid extracts. Tinctures, wines, etc., may be Feats @ concentrated at as low a temperature as possible (neut ral- ized fi rst, if necessary) mixed with saw-dust, dried an tgeated with the modified Prollins fluid precisely as in (294) . Coniun. uit of Conium maculatum is gathered wnen full t green, the yield of alkaloid being gree time, It is small, roundish ovate, laterally compressed, and grayish green. The mericarps which are often separated, have five jagged ribs but no oil tubes; the flat side or commisure is deepiy TFurrowea, giving to a transverse cut surface a reniform outline. Almost odorless and pemene? Ss but when triturated with a Peru y sen of caustic potash, coniwa emits the peculiar, mouse-like odor, characte ristic of the alkaloid, conii1 * which is developed thereby. 502. The volatile alkaloid coniine is the active Peng) dL ent of poison hemlock, occuring in all parts of but most abundantly in the imuature fruit, only part recognized by the U. 5. Tharmacopoeia. Many specimens of coniiumleaves and not a ¢ few of coniium fruit are almost inert from loss of the et jose ts LILE plant Oy which is the a +L , a routed, = ; Chen, OL rougnsly EStin- ) & - volatile constituent. Some method ae one alue of the crude drug would be of Bt a value. The strength of the odor developed by 1] drug with solution of potassa, becomes, to one ved with the use of the test, a read; means of j udg ing the relative, if not the absolute value of given sample fat fest serves at least to condemn a drug greatl in alkaloid. 303. An assaj ticable by the following process; prescription viai, 12 grams of the fi Add 100 c.c. of the weaker Prollins mi weil i ie vals for Bae hou, dur } aid of a mechanica ang he clear liquid ‘exact y C nal drop by drop, just sufficient to render distinctly acid. Jissipate ether by a gentle heat, add alcchol 15 c.c. and set aside in a cool place a few hour ar 2s as Sulphate. Filter, wash r B4¢ alcohol, concentrate fil + rat e and was that free acid is nearly neutralized gentle teat to 5 c.c., add 3 C. C. water and a few drops of dilute sulphuric acid. Wash twice C remove traces of fatty matters, reject 304, The one a may now ther the alkalimetric or the i add sodium yea onate in excess th three successive port i OlBy LOG. «Ge, sor, ether. (1) Treat with eth exsiecated neut mat ca. Le ium Sulphate to } roplets of alkaline, water, and titrate with standard acid, Y..£=29 or N 1-100, using iodeosin as indicator (165). Cal culate coniine from table of (94). eg Ad d. to the ethereal solution, drop by drop, sufficient 5% hydrochloric acid to supersaturate, avoid- i} much excess; dissipate the ether by a gentle heat ii > P] a tared evaporating dish with flat bottom. Drive off the excess of id by evaporating twice with a “a ttle alcohol (2-3 c.c.), dry a few minutes at a i BArene TAI ture not exceed- ing 60 degrees C., and weigh es eSidue of coniine hydrochlorate. After weighing, keep in a desiccator over Sulphuric acid an hour and we on a to make sure that the drying was complete. Multiply by 0.777 to obtain the weight of the alkaloid. 505. Alterative Method--Moisten 12 grams of the d rug with an equal weight of a 5% Solution of crystallized sodium carbonate, place at once in a 31 1itable flask, add petroleum benzin 100 c.c., shake well and macerate with occasional agitation four hours(or else pack in a per- colator and vercolate to 100c.c. with benzin). Pou or OL 50 c.c. of the clear liquid. Extract the alkaloid by shaking out with three portions of acidulated water, 5, 3 and 3 c.c., wash the acid solution twice with 10 c.c. ether, to remove traces of fatty matters and then procecd as in (304). 306. In absence of iodeosin indicator, the alxali- metric process may be carried out, as follows:- Wash out the alkaloid from the acid solution in (304) witt petroleum of 25 c.c. unite all finally, 10! ees. of cochineal or reaction sho benzin, in place of ether; in each. “lash each portion with 3 in a separator in whict q standa ra dad N Bre Zike id not ac i-25, indicato add wood be acid, - ae) a ee w Ori tne to make it so persistently after shaking. Jre ie agueous fluid , wash the benzin with two successive por tions of 5 c.c. water ich is 7 added to the al- kaloidal soluti to the point of exact neutralit; standa rd 1-25, and su tract the quantity used f roi standard acid. f 7 \ 307. K. Sehwickerath'\”+/’/treats 10 grams of the with dilute Prollins mixture in the usual way, filte c.c. of the fluid for the assay, adds 8 c.c. of wate 2or3cec. of dilute sulphuric acid (275 per cent) evaporates. The acid fluid is filtered into the per (9) and then hed one hour with ether, the solution mad alkaline with sodium carbvona te uenid again washed with ethe for three or four hours. Final tandard sul- phuric acid N 1-20 is aaa), the pated by wan ing and the excess of acid titrat n standard soda solution N 1-100. The extraction of the alkaloid would be much more speedily and perfectiy accomplished by introducing into the flask, the standar§j acid; 20 or 30 minutes would then undoubtedly suffice (S27) he process is faulty in that some ammonia must surely accompany t coniine. 303, R A. Cripps(®5)exhausts the conium fr by ] t D3 percolating 5 grems of the powder with a mixture of 25 ¢.c. alcchol, 2& c.c. chloroform, and 10 c.c. chlorofon Saturated with hyd roch oid nt acid gas and then extracting for 2 hours in a Sohxl tube with the percolate. When cold, the solution is ss pert in a separator gucce sive portions of 25 c.c. of water. The aq lution is treated with several small portions of form to remove coloring matter, etc., eae alkaline wi sodium carbonate and the alkaloid wash out with three successive portions of chloroform. The Oo uaa a solut 22 + q 8 Lor A; tempe rature not ing is checked sil y means of P< a6 7 or samol 1QL ait € Ve it of yer “7 + © Col YS 6 7 = aLer - ee e | ~~ & carbonate and ab "he < 4 " let Sepa vate ana i ed a separate retum the benzin sevarate and transfer th 2, shake let separate, @ Gontvaining 2 or 5S ¢.c. separate and reject the the acid solutions with wise the fluid extract m .dding O.1 gram tattaric ducted according to (303 generally are ven solved in dilute a = = 1. grams sh 0 ould conta. Ounce U + aecan solut \ 90 Py, v 50 c. 4 Vv 10n der ree it raticn 7) e jt. ae ee: ae ae ae iy a SP tua Swi WO ame LL, velvety fragments the lower surface th a) e < 7 ~ + 2 ck a ; a i | _ upper, softly pubescent, espe Lily an pS 3 veins; the midrib is prominent but not so much as in hyoscyamus; the venation forms she s upper surface of the leaf, the principal veins joining ne midrib at a very acute angle. 3135. Adulte rations--Other dried leaves are often : = - +} Pe ey eaten 7 7 ares < = ae +hne mixed with digi talis. the ahaa 2st of which are thos << — VS 4 of 0 al h of mullein, having a thick coa those of Inula coryza and Inale ¢ tire instead of crenate or serrate m fins nd the latter; 1, a 5 “CFIC ‘Wailale @ alley a having its veins branching off the midrib. f ve Ta ee laahe = ee ed eae L S14. Constituents:- Lhe exact corm position o1 4 + oc 1 . lane 4 . 4 in alcohol A deposi Le S$ a@ sediment from the aico=- holic preparations of the leaf) 1l but the last are glucosides. z Mh - eee ee ee ee ere Wath =9 SY ESTA See ny ee ee 315. ne assay process of Keiler 1s tne oniy one now : eke a3 Car tivilva npr Fg ee i ROG ys <= accepted as reliable. He believes that for practical pur A € poses it will be sufficient to dete mine only the active constituent and e Ul s content. procedure is as follows:- Exhaust 20 grams of the p ed leaves with 70 per cent alcohol by percolation. Evapo- rate, dissolve the residue in wate rand add solution of lead subacetate in slight excess. Rem love the excess of lead from the filtrate with sodium sulpl 2n lkaline with armonia, and shake with seve ral successive portions of chloroform. The chloreofom solution upon e- vaporation leaves a residue of crude digitoxin, which should he weighed as such, then dissolved in 3 ke chlorofom, the solution mixed with 7 grams ether and poured into 50 grams petroleum ether. The Bi pdt excite sege¢resates in flakes which are 1 to separate by vigorous shaking of the mixture then collected, dried and weighed as pure digitoxin. —— Ow ae Bias S16. Digitonin may be collected from the aqueous solution afte r shaking with chlorofom, by expelling the ammonia, acidifying with hydrochloric acid, precipitating with tannin, dissolving the tannates in 50% alechol, add- ing lead oxide, evaporating, extracting the residue witl dilute alcohol, filtering and evaporating the filtrate to wryness. Jigitonin, however, is of no medicinal use. 517. Digitalin (one of the active constituents of as sul. pl a Sed ¢ LCOnol , bo?! E Yap wi 2 OW l cok WT Uli Cu : : aoa eee tar 4. 7 Pre ving in tne 1) ra : Asi lie The 4 1 a 4 J ee talk, and the +na ane ~afoiwe 4 >> sAe ape yravure mek mathe. +he fF eiites Ore, Le, 2 YULG.F - = yee 5 “ a al +. lice expressed Db; sits a sediment, Ween ote C4 ia Mise ZAO 1 a4 ae Net eas = a Lve Hlate yium i 3 DLECES Ol wi Ye $ > AUD, 5 ln Sa ae - 7 + ~ =) =. rad cs : + + ¢ - LIiPMu Ana t rlat 3 DaLe l len. iTores Ly i r x ee rd + = a a on a gra yy Lignt putt 4S Ait becomes old L Pn ae 7, a wt ; “ht die ie a arma} ~~ a+ nae - th (ir - : - 2 Siurace tS COVE rea With Smain CYYStaLs OL Cua , Oat ) seta scared 4 sme) + - J acrid and exX* rene bit yr, au ic] itutes f i } 5 - 4 V¢ ry} 1} ] 4 i js 7 ok Lad Woke Lh) ake & i - 2 oform and ho alconol ; ry “ at | + + t | i Co i Pe crucible 0.25 grams oug ne o weig 29) ~ 2, + sr . ya ote Y : OGorlace EMmMiINnNasclioy Oe ye ilie Oa SMa Ld D ce » + 7 : Ps. } ae 1 § if as: ch 3k 3 ‘ t ls Of SiC a Y ug th auras H OWae Yr W Uil So © aGis = Oe 7 ry er nH Yi aa t o> \¢ > } =) ot c ¢emnea yo} r¥ pn chloroform and mace rate half an nour, atv a tempe racure Os a hy 55 : @. m +. 1 + = 7 a a Pe about 55 degrees C. ransfer to a small filter, and when = L \ the chloroform has all passed, percolate on the filter with fresh chlorefom to complete exhaustion. Kvapo rate the solution in a tared capsule, dry at 100°C. and weigh. Dissolve the residue in 15 c.c. ether added at once, Granate r immediately to. a smail tared beaker, cover and set aside to crystallize. It will be found the ether al- way 8 fo ms momentarily a perfect solution of the residu from which crystals of elate rin have begun almost ie ately to separate ar eee After a few hours, decant the ether into a second tared heaker, and allow the ether to eva in til reduced to about 3 c@.c. Decant the eae ethe | Y into a 3rd beaker, rowan the cryst ede whi ea. 7 a . ‘ = y : = 3 - Yash these with a Little ether DY decantation, Allow the *. —~ ~- = A od ~~ AS ww A + 40 ey 4 V rh oO rely, add 3 ca. ine residue r refully wash =) I a i aaliys dry all the crystals obte ether in the 3rd beake Yr ee None te enti of ether and obs 13 mains undissolve with a Little et : Aas ured os m1, rh he elate ri: 1c 3787719 ; ea ana welgn 1x toa of Ne €Lave rin 1S UsBsUa@LLY . ai one half that of the original ehlorofomic extract, Ii Ps Fea | mriah eal a] 1, $4 4 ra) ~S we 2 Le Yn falls much short of CNiS, jtOSS ai the elaterin in Ne Cc crystallization to add an arhity ium of good quali crystallized ela re § ry correc sti ten mil rams. Fl t a cake S may be expected. In any 3] on o 1 ield 16 to 20 per cent o ERGOT. ye Sais The of fic Q A/F GOL GL/5 3 ) \ ia] erent r ve al ergot of Rye 1 Y} in diameter. it nt long and from 2 to 6 mm. (1/12 + @ be = ° On other ¢g rasses, it eH usually of ize. Triangular, slightly curved, tapering toward, obtuse at, the ends; exte mally, purplish black, int nally, whitish with pink lines; fracture shoot (not brittle). If a portion be macerated in water cont ic potash or soda, then carefully caus P blade or spatula, the fragmne) of mycel plainly disce mible under the microscopy ly in powder or where triated with an unplea sant ; taste oily and disagreeable one, year old, it is unfit for ise."Old with a sharp snap, is almost devoid of ae =) A. Yee ee | eoitiee . as ok on lL. - _ ~ |. 4p ~, + £ tne fractcunr is hard and brittle between the eevun ana ‘ - 3 le ee eee net+eal . Dimer tad tre ; aol comnvna ravive odorless and tasteless ; BHOULA Dé Fre ce mos€ recent study of errot is that made b 7; : contains but one alkaloid, and that this is the active principle of tne drug. This ie ae cas wWonich Keller be- lieves to be i dent tical with Tanret's ergotinine, Kobert comutine and Dragendorff's picrosclerotine, has the following characters: It is insoluble in petroleum-et 4 which precip yitates it from its ethereal solution readily soluble in alcohol and in chloroform, but dis- solves only with difficulty in ether after it has been > aAlviioc m = oe | ~~ Lae = ee Wy | een a crystallized. lhe alcoholic solution has a st rong bluis} violet flourescence, especially after acidulation. The ee a | e _ aris = —- . — a ire ye 4 ott ~~ = NeEWUG Tras Balt U are radi Ly s0LUI VLE LI Cuue? t. rie aCiGd oc ¢ oe iwalry tan wric«r an ti eee what 2 ee ie Sa } OnLY Spar Lri¢ LY SO. From a somewnat aciac So0Lution » COLO {* . ; o + ¢ } nin? 4 . Vs oy we Pt th, Lee = Lom extracts the the alkaloid; ether removes but little 8s from 10 to 30 m.m 4)who arrives at the conclusion that ergot ZO Sao ir esa of Keller: Donk al ama) 525. Assay process of Keiler:- Pack in a small nNewolator. 2H crams f pe YT OLG, VO {I 9 —YVe_E LS Hhaust wits et roleum Si BO CeCe cHaneney nh minute 5S, rah mixt Ure aL EYaiis CG ! NESBA eters U 3 @ ere Shake the 1aixtu re well 2 3 re ae y during half nour. TOA ES SE ere Seay ethe real solution or as muci — ~ : +, mM Geena are hg representing one gra Of URE three successive porticens of acidulated with hydrochloric portion of acidulai water al to ascertain whether the alkai The mixed acid solutic € ammonia and shaken cut with t SOewe ss and 25 ‘cen of ether, tared flask, treat the residue 4} gC EES Git : Coes i Say Ea ee ae as = ethe x 9 2+ NQ@tLLy ay tO a CONSvtaNnt Weigfnt and Weign.e « E> ZO a 3s L 4 ae 4 c ee 5 Ss YIaO~6 Chil QO YO OY 1s @ petceYr soi t i i © Tit Ch tA 4. +han asthe y» WAIVT a Tiahle in fr YT nheting ~~ wm leq ons: yileeli Cuue’;r, tet & tS oe ho 4 OP Bi x 7 @) 1E aK © e | JGR VAILAaAvLES CLIALALOAOTIS » } oe i as + os _— - m2 + - nyt ++ - a 7 3 nence e~wmer 15 preierrea ana NE QUuUaNTILies pre escrivpea JeAD) ot ch haa been kept in powde, sondition, 0.165 per cent was obtained., showing the drug may be kept for some %i without becoming inert. Old ea ee may | jishea from new, by the color of the ether ¢ n thie €itlovr= former is dark brown, in the latter, 328. Physiological test of Ergot:- Cwing to. _ the ex- isting uncertainty conce ming what is the real active principle of ergot. Fobert and “Grunfeld aa eae ee a physiological test of the ac aus ty of the drug, by feeding minute quantities ar the sample to roosters. The effect an active drug or preparati ion is p romptly shown in the comb and wattles ae the fowl, which assume a characte ris- tic dark color from the peculiar action of the drug upon the capillary circulation. The two methods of assay, physidlogival vs. chemical have caused no small discussion but the chemical assay upon the quantity of contained alkaloid, holds prefe rence. 329. The rhizome and roots of Gelsemiun are the parts of the drug officinal. Cene light and fibrous cylindrical secti ons about, length; exte mally of a brownish yellow co 4 3 lor, slightly wrinkled; tough, breaking with a fibrous, splinter S fracture; ba we thin, with silky be vee’ rs, adhering to the light yellowish, porous, b road-? rayed wood; pith 2D, | itte ¥y > odor slight; taste pe rsistently ° capable of yielding crysStallizable salts. I soluble in petroleum benzin, freely soluble in still nore s¢ in chloreform. This is accom alkaloid whieh seems not to preduce crystail and which, like amorphous quinine, seems always or less colored. The aie contains a fluorescen ple analarrous to aeseul but regar¢ as nee relsemium and called Pate eminmic acid. This i8 removed from acid solutions by thorough washing with et] chlo refo m, but a portion of it is almost sure to accom- pany the alkaioid when extraeted’in the usual we 551. For the assay of the drug, Lyon's short Proces (71) to (74), the alternative of (72) being prefer ably followed. The alkaloid abtained is of a dark color and is of complex conposition so that alkalimetrie titre tion rather tr an i xeet weighing is to be relied upon. The l > 30 Yellow jessamine Pg at least o + other or S titration equivalent may be tak crystallizable alkaloid, hence, 1 c.c. of ordinarily employed in alkalimetrie titrations is assumed to neutralize 16.3 m.g. of alkaloid. 2¢ , 2 + 74 - - < 2 } Fe $32. Titration with Maver's rearent:- The acid s0- lution of (72) may be titrated with Mayer's reager : 5. a ag patos Din z eA oe results almost. as satisfactory as those by aci Ne Since in either case, the equivalent factor is : assumed, and we know nothing as yet of the relative med- icinal AC ctivity of the several alkaloids presumably pres- ent. Perhaps a gravimetric determination by weighing +l precipitate produced by Mayer's reagent - the acid so- lution will give as good a practical measure as any we can rwach with our present knowledge, of the vale of the sample. 533. Assay of Galenical Preparations:- ] tract may be easily assayed by the process of (150 follows , the determination of alkali oid being final mad by alkalimetry as above. A purer alkaloid is obtained by the process of (149 b) ana fora gravimetric dete rmination ao he lL is Se . = = inne vY oe | , this plan (or that of Farr and Wright, below) shoul ; - Ta m3 nia 5 + F " adopted. lincture €CtTCGe., ar ) ead on rere y32, | Y) nec Tey oa a ( 1 7 2 } \ - C2 i’ + : ZB D maas of Parr and Wricht (85 ) e WEL | : gn DWI, YYOCESS OF fhaYrYr ana Writs = = H itt. Gy Cie Ot a tincture or 10 to 20 c.c. of a SVapo ated on a water bath, to a small rat necessary to remove all alcohol. en coo add 1 G.c. seminormal sulphuric lt through absorbent cotton into a dish and filter with a little acidul acid fluid with three portions of chloroform, which in tum, are added afterwards to the content , m the aqueous solution alkalin ith three portions (: chlomfom is then (5 c.c.) of water co phuric acid. The ae; Boru ions are uni’ s of "| Warner's reagent (1 ; il the precipitate has s S45 The fluid } | er, the filter washed witt little water and then 5 c.c. of a 2G, BS ay : a az Soiution of su the flask containing the alxkaloidal precipitate. The fla: is allowed to stand with oceasional agitation until the alkaloid all periodides b wholly decomposed, as shown absence of dark ored particles. The sol is then filtered, flask filter washed, first Gh 2 & GeCe Of Sulphurous acid then with water until the wash- ings are no longer precipitated by Maver's reagen Fil ,yate and washings are made alialine with ammonia and Shaken out with three successive portions of chloroform (10, 10, and 5 ec.c.), the chloroform evaporated the resi- due dried at 100°C. and we igned. Guarana and Kola Nut. 556. The active constituentg of guarana, coffee and tea is caffeine (or theine) which is also the constit of kola nut and of mate or Par Aa. a: pO The ta LRALS Le is very fee b1Ly nasIiC, 60 tha f cannot determined b7 alkalimetry, at least with any of the indicators ordinari- ly employed. It is not precipitated by Maver's reagent, although a characteristic erystalline precipitate is pro- ome duced bi a solution of pany lodide saturate a Ww mercuric oxide. In an acid solution, it is precipitated by Wagners't reagent (15) and it is also precipitated b; tannin. 537. Caffeine is soluble in 80 parts of cold Oo i \ in 9.5 parts of boiling water, also is freely seluble in | ; “tf, } 4 j , eold aqueous solutions of cer : Salicylates and benzoates of the alkalies; it dissolves in 33 parts of alcohol in 555 parts of ether and in parts chloroform and it is also readily soluble in benzol and in carbon tetra-chloride. It is removed from watery so- lutions even in the presence of free acids, b with ehloreform, although not so readily aa wi lution is neutral or alkaline. Jt cryst 4Si- its solutions in volatile solvents and may be easily sub- limed without alte ration. y Shaking - anh f BON ] = oe ee : SS ee 538. Moses mada € rEg' 86)/has shown that the alkaloid can be determined with a fair degree of precision by a 1% ric process involving its convertion into «a periodide. His procedure, appli cable only in absence of other sub- F Stances p recipitated by jiedine, is as follovs:- To 25 1 3 on Pn a , ee) ec.ec. of decinormal iodine sclution (U. S. P.) ution of the caffeine acidulated with hydroch the quantity of caffeine not to exceed 25 mil (122). Make up the volume with water to exac Shake the mixture well and let stand unt il the separates so as to leave the supermatent fluid (This must be of a deep iodine red color, othey experiment must be repeated, using a smal the caffeine solution). at 20) ChiCn he clear flui and titrate with decinormal solution of sedium thiosulx deduct twice the volume of ‘the thiosulpvhate solution re- quired, from 25, and multiply the remainder by 4.85 to find the weight in milligrams of the caffeine present in the portion of sclution used. fj ~ ~ a 339. Jn many of the older processes for extract f? > 5 + wre 16GeEnR , hs « Hann e | AP lho + +1,5 4 a caffeine ; lime was used. It has been shown that this in- yolves loss of a portion of the alkaloid, hence it is no admissable in any process. Mapnesia seems to be open to the same objection, and no direct loss is occasioned hb the use of oxide of lead, oxide of iron, alumina or basic lead acetate, sag some alkaloid may be withdrawn from a solution by occlusion in precipitates produced by these agents. 340. The method of J. U. Spiele J158) is well adapted for extracting caffeine from aqueous es tracts o t,} preparations not containing chlo roph +2 given for fluid extract of Guarana’ Big as ( Into an appropriate vessel (preferably a flat-bottomed graduate) pour 2.5 c.c. of fluid extract of C 2e5 grams of a mixture of equal amounts of dry ferric hydrate and sodium bicarbonate, mix well, preferably with a mechanical stirrer, add 10 c.c. chlorefom ana stir well together. Should the magm rema i wlocculent and the chlorofom not separated therefrom, add a sufficient amount (10 to 20 drops) of a mixture of equal parts glu- cose and water and incorpo rate thoroughly. Decant the fl chlorofom into a tared beaker, Repeat the treatment with two or three f (Se.ce) of He sh chloroform. (Should the the sides of the graduate, aed: wag stirr er, scrape it down occasionaly). Fi » evaporate the chlorefom, dry to censtant weight oe erties: 541. Process of Pet Te rrat(&8) (F -woposed for the assay of tea, but stated by the authors to be equally appl icable to quarana or kola). Treat ten grams of powde rec tea with 30 c.c. boiling water, mace Eee 15 Minutes ther evaporate on the water bath until the i] peared, leaving the powder visibly and unifc a small percolator and exhaust with v) ts a ry A ~maliatian mwntil Tae peewee w rCOLATION until @ few aropvs of al t Liaw j a Se S ) S Ly { p> ob i Me with hot : ry cr — ndition gene “\4 o > a ee . 4 L = pure eno sepa atfirm ha = cd ~ tanaon ~~ . + Form extrac s.enedad powa , vxle WnhotLe of the z eine , une LSE ; wLAMe, monia peeing 542. An tne apo WouLad cone sist in mace: fe : zr witl 00 Cs.C%s cnlorofom with frequent o: onstant Shaking several hours, decanting to 5 t 1, evaporating, tak- ing up with rags i and dete rminin; caffeine by th thod of Gomberg. In applying the to guarana or mace ration with warm water would, no doubt, be better than boiling in tl step of the process, owing to the presence o0: 545. Guarana cannot be so conveniently exhausted boiling water on account of the starch it contains. It better to exhaust the powder, 10 grams by percolation witli a mixture of 2 volumes of alcohol and one of water, ob- taining about 1.00 CeCe percolate, evaporate the percc 1 yacetate or sufficient to impart to the mixture a sweetish taste, make up to 500 c.c. and proceed as ii Su 8) remembe ring : ; a one gram of the drug. 344, DrB. Dohme and Eng 89)direct to boil the powde red kola with a mixture ohol one volume, water 2 volumes, three hours, ina ror con Aeneex. Filte vgs evapo rate bath, mix with calcined magnesia and sand lry complete and extract by boi chloroform. Schlotte rbeck (90) simply extract kola with chlorofom fo c } to dryness on a wa ten hours ins a Soxhlet 9 use a very fine powde of slaked lime and 20 c a water bath to 14 gy successive portior ( re of alcoho i Cao k Sr HYD RASTIS.~ ee 346. sis are knotty Nicsd; on the uppe Osi- tions an ie se scars ( cuplike p roject eat "solden seal". Externally Ss Ov color, amulate internally of a resinous fraction; : na rrovw wood We iges, from a large 1 & woody center surrounded by a th cal tissue, which is-bordered by cel Ls. ah > 547. Constituents--The alkaloids- “A A principle constituents. Berberine is i Nid ted in nature, being found in at least VIL RN orders; it is present in berberis, cop \ \f menispe rmun, pina ea ete ydrasti SK ®) yy, . : Ie es colorles very bri Lidant glassy crysta. «* 3} . + =< ee nis a a ites L rule nowever, tney are white and opaque, presence of nume rous fractures. The yellow color of the KRIN be ss Pace adie res very tenaciously to the hydrastine, so WY with the active principle. This o- noid is made by pre- . \ Se epi a concent rated alcoholic zxutskixy tincture of Sah hydrastis with acidulated fates. and i8 probably in the ee mein, an impure muriate of be rpe rine, Hi drastine and e y= : N be rine howeve r, are the constituents upon which the valu Nr of thie adyrug 18 examined, Sie ee .Y- Thompson \ 10 grams of the weg in mode sobatie fine Vp nausted with strong 3 hours, percolat same menstruum, 2 fiask, 1.5 c.c. hyd Sulphuric acid and allowed to stand 2-¢ shaking. At t) counte ro oised aoa of eq ese volumes until Blase giv 105°C, weigh and ine and then multi , j ote Cee hk a3 : b 4 O I to 100 c.c. witn the place pA D t ] a cn © 34 pei e : FS re % ad 4 1 ; SEPA rave e 100 & rams , Ings s O ¢ rams arug ar OuvedG ft - 4 i © +3) , aa Ps ee With AlLUTE SULPHUric a@C1ia off into a sepa rator, yy" a vas a es +e . aval Y¢ wT 4 } anyon ny 4 og t+ te LO extract tne alk al oid, mage alraiine witn ammonia aite; separated from ethereal solution, and finally extract with ether. Evaporated dried and weigheé, the yield of crude alkaloid is then dissolved by the aid of heat in 8 c.c. alcohol and 4 c.c. ether and then 20 c.c. water ¢ ye . < > af vw etary PA Wn an aicteem seas) vatetes Slniew cuwitot 3 after stan ding a NOUTS aALMOStL tne entire u - her ot 5 v=) or 4 Te aren 2} ) . . “ ao + a of hvdras ne will have washed out, 50 Gat ¢) cr taté . nc ¥ 7 waah } ei + =} _ da . ry P Ns re moved 10 a@ ie He c I» W2ENnea Witnh ano it O Gele ,OuG went 7 ye + sary isfer sn ,ou ge a. , > <] ee | ; wate » ,vransferred back to flask, dried anda CI Plo Qe Ry re FE} = : -) + G4 ¢ 2 ~ 4+} 1 a VULe Tee Ve HDC Wa rv ¥=/Dp Proposed née ToLlLowing:-- n + ‘3 n>» ) a] > a = - 2 | ex aate 4 _ ? P Into an arlenmeyer flask of at least 4 oz. i Nite LLY, 46 iy ig f +} Bat a Vinee ti Laie s v K's €avd ( ef a OT LLLe LUAG ae 2G Yac % to DE assay >» ? Doses to cr dans yr in se Teal ~ tr Te) i 4 a ¢ s =) = ee f t 4 1 as hie : » ~4 ™- z P <2 ° ; “ial of + E Gy or ~ \' “ m4 < multiplying the number of c.ce of 1/2 normal potassium iodide consumed by 0.167125, the percentage of anhy- drous berberine in the root is obtained, as 1 «ec. of the potassium iodide solution is equal to 0.0167125 of berberine. 357. Proportion ofbAlkaloid ---~ Good samples of hydrastis contain from 1 to 8 percent hydrastine 2 to 25 being good average; of berberine from 1 to 3 per- cente Standardized perparations are based on 2.6 per- cent hydrastine. 353. ~-33 Ipecac 3: t-- The roots of Cephaelis Ipecacuana reach us in broken sections about 2 ine long and from the thitk- ness of a straw to that of a quill. Externally dull grayish, reddish or dark brownish, depending upon the variety, prominently amulate with alternate thickening and constrictions, the rings, numbering about 20 to the inch, usually. not extending around the roots, however. Fractur, short, granular, exibiting a thin whitish or grayish woody cobum surrounded by a very thick bark (constituting at least 75% of the toot). Odorless in entire state, but the powder (light-reddish gray to brownish gray in color) has a nauseous odor; taste nauseous, slightly bitter, and acrid. The wood is inett > Carthagena Ipecac is a variety from Columbia, which has crept into our market to take the place of a very scarce Rio variety. It is of a dull gray color thicker less frequently and sharply crooked, and lacks the constrict- ions characteristic of the Rio Ipecac, a@ though it hears the annular thickings. 259. Until recentmly Ipecachas been credited with but one alkaloid, called emetine, the researching of Pawl and Gzownly have however shown that the emetine heretofore known consists of a mixture of two distinct alkaloids, differing in physioogical and therapentic action. To these alkaloids the names Hmetine and Cepa- eline have been given, the foremer being regarded as the expectorant, the latter as the emetic principles of the drug. 360. The following (109) is the method employed by Paul and Cowhley for the complete assay of lpecaci-- Mix 50 grams of freshly slacked lime moistened with water, and extract by percotation with amylic alcohol. Extract the akkaloids by shaking out with dilute sul- phuric acid, make alkaline with anmonia and shake out with ether. The etheregkl solution is to be evaporated and the residue litrated with seminormal hydrochloric acid, of which one cec. witl neutralize 124 milligbams of emetine and 11? me. of cephaeline. 361. The Hydrochloride solution is mixed with caustic soda in excess and shaken out with ether to remove enetine. Sdéme eephaeline, however accompanies it, so that it is necessary to bring the emetine again into acid alfueous solution amd repeat the treatment with soda and ether until the residual alkaline solu- tion is no longer clouded by adding ammonium chloride. The purified emetine is finally determined by titration with staudord acid. The cephaeline is obtained by add- ing to the residues containing it ammonium chloride amd shaking out with ether and is also determined by alka- lietry. $62. The further studies of Paul and Cowley show there is a marked difference between Barzilian and Carthagena Ipecac in the relation proportion of the seceral alkaloids they contain. In the former the eme- tine constitutes about 70% of the whole, in the latter only 40% We cannot therefore consider the two drugs as therapentically indentical. 363. For practical purposes an the present state of our knowledge, it is sufficient to aigedes aes the to- tal content of alkaleia . in a sample, the rien Bra- zilian or Columbian, being always jae OR 1€ a5- say is easily made either by Kel a7 he method 43), or by Lyons short process No. 2, the llowing (72) by that of Grandvel and L&joux (45) or hat of Crippo and Whitby. 364. In the short assay process No. 2, ether alone may be used instead of a mixture of ether and chloro- form. In the following Keller's process use lw grams ipecac, 90 srams ether, 80 grams chloroform and water of ammonia 10 grams, finally 10 grams water. Pour off 100 grams, extract with hydrochloric ald again with ammonia and a mixture of three parts, chloroform and 2 parts ether. Whichever process we may adopt, we may finally determine the alkaloid without purification either by tittation with Mayer's reagent (867) or by alkaline, taking titration equivalent to c nventional number of figure 254 from (94). Ra. Cripps and A. Whit- by (101) use as the internal solvent either containing one percent of glacial acetic acid or a mixture of ace- tic ether, chloroform and ecetic acid, and adopt the following procudure:-- shake down lichtly, drench with menstrum, cork the up r end of the percolator add let macerate over night. Wash the acid solution once with ether, followed by two portions (6 cece) of chlor- oform. Evaporate in a current of air, dry in a dis- sicator for six hours over suplhuric acid and weigh. Finally determine alkaloid columetrically with Mayer's reagent, 866. K. Kathmayer (102) directs to digest 15 grams of powdered epecac (air dried) with 148 c.c. of 90% alcohol md 2 cece Of hydrochloric acid, spe gre 1. 12, for four days at 40 degrees C. with frequent agitation; after cooling, measure out 100 c.c. of fluid, mix with 20 cece Of a one percent solution of lead acitate in dilute alcohol, add 1.5 grams of slacked lime, evaporate to a pasty consistances incorporate > grams of powder- ed glass, dry on water bath with constant stirring, ex- tract the alkaloid by hot repercolation (10 hours) with chloroform. The crude alkaloid left on evaporation "| the solvent is dried at 100 degrees C. and weighed, | and then treated with 2 c.ce of normal hydrocholoric acid, the insoluble residue matter washed on a filter, dried and weighed, and its weight deducted from that of the erude of the alkaloid. 366.& 367. Mayers reagent has been much used in determining “emetine", but without discrimination of the several alkaloids present. Practically no dount, when the titration is made in a properly prepared solu- tion, the results are as trustworthy as those obtained by other methodswhich determine only total alkaloid. The figure given in the table of (119) may be adopted as giving a sufficiently close approximation of the truth, if the fluid titration contain 2 to 5 parts alka loid in 1000. 368. Metnod of Kunz. (105) - 8 grams of fluid ex- tract are diluted with’8 grams water in an ordinary vial, 32 gms. chloroform and 48 gms. ether mixture fre- quently agitated during half an hour. After sep atation 50 grams of the chloroform -~ evher solution represent- ing five grams of the extract are poured on g@iltered into a tared flask and the solvent distilled off. fhe varnish like residue is twice treated with 5 to 10 cec. ether and evaporated by forcing a current of air into the flask by means of a rubber bulb, after the last trace of the ether have been removed and the residue dried on water bath, it is weighed, for the titration, the alkaloid is dissolved by aid of heat in 10 c.ce ab- solute alcohol, and sufficient water added to give it @ perenant turbidity; after adding one or two drops haematoxylin solution 2/10 H.C.L. is added until the violet red color changes to a pure pale yellow. Hmetine according to Kumz is diacid and has the molicular wet. p 508. Hence 1 cece n/AO hydrochloric acid equals .L254 ! gm. emetine. | 369. C. C. Killer (106) has improved the methods and offers the two following:-- (1). 12 grams of powdered ipecac deprived of fat and oil with ether transferred to a tared vial of 200 c.c. capacity, extracted with 90 opm ether, and 80 em. chlor- oform, and 10 cece water added and again agitated for two or three minutes. 100 ems. of the clear liquid are dicauted, the solvent distilled off, the taken up twice with small quantities ether (to remove 15 minutes afterwards the last traces of chloroform), heated for on a water bath at 100 degrees weighed and titrated. (2) 12 gre ms powdered ipecac are Placed in a 200 Cec. vial, agitated frequently during 5 minutes with 90 gm. ether and 30 gm. chloroform; gies adding 10 cece wa- ter ammonia and allowing it to stand one-half hour, 10 Cec. Water are added and 100 int of the clear solution transferred to a spparatory funnel where it is agitated with three successive portions of 25, 15 and 10 c/ c. of 1% hydrochloric acid. The acid solution are next transferred to a separating funnel, made alkaline with ammonia and extracted with two portions of 50 gms. each, of a mixture of three parts chloroform and two parts ether. The alkaloidal solutions are filtered through an ether wetled filter into a tared flask, the solvent recovered (The last traces of the chloroform removed as before) the residue dried, weighed, and titrated as above. $70. The British Pharmacopoeia directs for the assay of + why extract ipecac, the process outlined in (149 b) which perhaps is as good as any. The main point in this met od is to have the solution quite dilute be- fore adding lead subactate. 371. Prescott and Gordin (107) extract the drug by any one of the general methods. In the iodometric estimation the total acidulated alkaloid solution is made up to a difenite volume, an aliqual portion taken, and added to the measured escess of the iodine solution, as heretofore discribed. The iodine factoris taken as fairly near the means factor of the total alkaloids. 372. Galeuical preparations of Bpecac may be eas-~ ily assayed by the usual methods. See specially (150) te (158). In the case of a soluble fluid extract of ipecac, we may advantageously dilute 5 Cece to 2 Cece with water. Take 5 cece if the dilutions for the assay, add a little hydrochloric acid and wash twive with ether, 25 and 20 c.c. Then make alkaline with ammonia and shake out tWice with ether, 25 and 2 ceCes once with a mixture of 15 cec. ether to obtain an alkaloid pure enough to weigh. Of course it is a quicker way to make alkaline at once and shake out with ether and chloroform, and determine alkaloid by acid titration If emulsious from resort to sawdust process. 373. The proportion of the total alkaloid in good ipecac is probably not less than two percent. Dr. Dohme has shwon that the “worry” part of the root con~ tains very little. Two percent alk: loid represents a very good root, and then the perce cent has been the one adopted anong manufactures of the standardized goods. _=-3:. NUX WOMICA AND IGATIA BEAN $:-- 374. The seed of the Strychnos nux vomica occurs in orbieular dises from 3A to 1 inch in diameter, and about 1/6 inch thick; flat or slightly convex on one side and concave on the other, with a sligntly raised margin on the concave Side. On the one side is a rid (raphe) extending from a raised point in the center (hilum) to a nee on the edge where the radical is situated (chalaza). Both smffaces have a grayish or grayish green, shiny, ern appearance due to a large -~] + > number of silky hairs closely pressed to the seed and forming a tuft around the edge. Testa thin, fragile, somewhat soft, enclosing two discs of horny, trans-~- lucent or opaque, yellowish ot whitish albumen around a large central gavity. The embryo is contained in the cavity, and consists of a short radicle and two flat, heart-shaped, veined cotyleduus extending about one- fourth the distance across it. Inoourous; taste ex- trenely bitter, powdered nux vyomica is yellowish gray, and has a faint sweetish odor. 395. The total alkaloids amount to 2.6 to 5 per- cent. They consist principally of strychine and bru- cine, the former being in excess. The action of the alkaloids is believed to be simular, but strychnine is mach more powerful. A third alkaloid, agasurin, has bee claimed, but in all probability it j imply a 4) mixture of the other two. A glucoside logs found in the seed as, put it exists in larger quantities in the pulp surrounding the seed in the fruit. Other constituents are a concreat fixed oil, gum wax, phos- tes and a yellow coloring matter. 3876. The seeds of the Strychnos igmatia, a tree growing in the Philippine Islands, where they are much esteemed as a medicine, and whence they are introduced to the mediaal world by the Jesuits, who conferred Yp- on them the name of the founder of their order. The fruit is pearshaped and contains from 10 to 15 of these hard heavy seeds lying one upon the other and imbedded in a dry médullary mass, but the seeds come into the market separate. Their shapes are various, owing to the manner in which they are situated in the fruit, put their general form is ovate, sanewhat flattened, and more or less angular, They are about one inch long but considerably narrower, and have at one end a smal 1 depression indicating their point of attachment ee Their testa is of a less silky nature than that of.nux vy omica and of a grayish brown color. In commerce they are perfectly smooth, the testa and hairs being removed t ++9 id the rubbing of the seeds against one another and ,erefore the outer surface consists of a dull brown or blackish horny albumen, translucent when fresh. The embryo is oblong, situated in the broad end of the seed, the cotyledons extending only about half the distance across the irregular cavity; Inodoraus; taste ex~ ceedingly ty at 3°97. The constituents are the same as in nux vom- ica, but in the different proportions, the strychnine being present in larger quantity than in nux vomica. Ignatia was once used for the preparations of this in- portant alkaloid, strychine, but rarely at the present day, as nux vomica is important insuch large quan itities and hence is a much cheaper source. 373. W. Ae Dinisten & F. M. Short have founc the follwwing process a satisfavtory one for the assay of nux vomicat-- (108) One part of nux vomica is made into a paste with a solution of two parts crystallized a@€odiwm carbonate, the mixture dried and then again pow- dered equal to 5 grams nux vomica is packed in a suit- able extraction apparatus and exhausted by 40 CeCe chloroform containing 25% alcohol. This is usually accomplished in one to two hours. The solution thus obtained is well agitated with 20 C.Ce of a 1% solution chloroform is much aided by gentle warming. After re~ peated agitation the chloroform is separated by means of separatory funnel, and agina shaken with 15 cece di- lute sulphuric acid. The mixture acid solution from Which all the chloroform has been separated shoul 1a be filtered if necessary, then made alkaline with ammonia {2s and shaken with 25 ec.ce chloroform in a separatory funnel. The clear chlorofrom solution is evaporated on a water hath to constant weight, dried and weighed. 379. H. Beckurp gives the followings-- (109) Two germs. of the finely powdered extract are dissolved in a mixture of 5 c.ce water, 10 c.c. alcohol. The 5 c.c. ammonia added. The solution is then shaken with three successive portions of 20, 10 and 10 «ec. chloroform, and united chloroform solution evaporated. The residue is dissolved in 15 c.ce n/10 hydrochloric acid solution filters and filtered, well washed with distiléd water. The untied filtrate and washing are then titrated with centinormel soda, cochineal being used as indicaton. Substract the number ¢c.c. comsumed of soda from 150 and multiply by 0.00864 to obtain the total alkaloids in 2 grams. The percent is then found by multiplying by O0. 380. Patch's Method (110). -« Ten grams of powder- ed drug are placed in a 200 c.ce erlemmeyer flask and dried for three hours at 100 degrees C. and then cooled ina dissicator. 100 c.c. Prollius liquid modified (ether 250 c.ce chloroform 100, alcohol 125 and armonia 10 c.ce) added to the flask, securely corked and shaken vigorously from 12 to 24 hours, best in Mechanical shake er. 50 c.ce Of the clear liquid are decanted from the flask into a separatory funnel shaken with 10 ec.c. por- tions of 5 percent sulphuric acid, until all alkaloids are removed from the ethereal liquid (proved by with drawing a few drops with a pipette, adding acidulated na) Water, evaporating off the solvent, and testing with Mayer's reagent), the mixed acid washing are placeé in a separator,made alkaline with ammonia, washed free from alkaloid with successivé portions of chloroform solutions evaporated in a tared flask to constant weight This gives total alkaloids and wet. x 20 givem percent. 381, Killer (111) proceeds as follows:-- Put into a small tubular percolator (18 om. long, 2.5 om. wide) 15 grams of the thoroughly dried drug in fine powder, exhaust by percolation with ether (remove fat, but this seems unnecessary) of which about 100 c.ce un-~ til be required. The ethereal solution will contain part of the alkaloid, which must be removed by shaking out first with 5 c.c. decinormal hydrochloric acid, then with three successive portions of acidualted water (6 c.ce Cach). The drug in the percolator is transfer- red by means of ether added to make in all 100 grams. Pifty grams. of chloroform are then added, followed by 10 cece Of 10 % solution armonia, and the flask is well shaken frequently at intervals during half an hour. The acid solution containing the alkaloidw removed from the ethereal percolate is then added, the mixture well shaken, and when the ethereal solution is well separated 100 grams. of it are transi n Erlemmeyer flask, the solwent distilled off, the residue treated repeatedly with a little pure alcohol to remove traces of chloroform, dried at 100 degrees C., and weighed. 382. The alkaloid in the residue may be determined approxinately by alkalimetry. Killer directs to dis- solve the resideu in 5 cece chloroform with aid of a little heat, add 40 c.ce ether, 10 c.ce water iodeosin findicator (1% alcoholic solution) one Serban then deci- normal hydrochloric acid 10 c.c. Titrate back with decinormal ammonia until a permanent red color aprears in the aqueous solution. (Cork the flask, agitate after @Cach addition of ammonia). Hach cece. of decinormal acid corresponds with 86.4 me. alkaloid, assuming that nearly 50%0f it is strychnine. The titration may also be conducted according to (90) and (91) 888. Schwickerath Method:-- (112). Macerate in an agitator 4 prams. of the dried and finely powdered irug, with 100 c.c. of the following mixturet-~- (2 c.c. ammonia 30% ether). Filter off through cotton 50 uc. (equal to 2 opm. drug), place filter in shallow dish; add 2 or 8 cece dilute sulphuric acid (2.5%), and 8 cec. Water; evaporate off the ether, alcohol and chloroform 7 a) 7 by H D Qs > 5 cr 1°) 9 at a gentle heat, filter the acid solution in perfora- tor and wash with petroleum ether for 1 hour. Then add 5 cece 5% anmoniap arrange a ring of cotton in per- forator and chloroform, the alkaloids their obtain are @issolved after evaporation of the petroleum ether and chloroform in 10 ec.ceN.1@20 sulphuric acid, and titrated back with N. 1-100 caustic soda. 1 cece. Nel- 100sulphuric acid being equal to .00864 pm. mixed alkaloids. The result times 50 equals percént, total alkaloids. 38& Assay of thedrug may be made by Lyons Short Assay process No. 2, using 5 grams of the drug in eas powder, and increasing in proportion of ch Llorof orn (ether 8 volumes, chloroform 1 volume) fell Ovincts preferably the methods of (72), The methods of the fol- lowing paragraph differs from this in some detail and is perhaps preferable. 385. Alternative process$-- put into a four ounce perscriptive vial 5 grams of the drug in as fine a a powder as can be made, add 100 c.c.e of a mixture of ether 3 volumes and chloroform 1 volume (cool to the room temperature before measuring), add 1 cece of a 50% solution of ferric chlorides shake well and let acerate 1 hour. Thenaddd 5 c.ce of a saturated solu- tion of sodium chloride and 10 drops pf 10 drops of 10% hydrochloric acids shake occasionally during one hour; add 5 c.ce solution of 10% ammonia, Shake vigons ously and macerate with frequent ar continous shaking four to six hours. Complete the assay by (72) to (74). The alkaloid obtained is nearly white and contains very little Anpurity, but may be titrated with standardize acid if derived, see (3882). 386. C. KE. Smith (1138) exhausts the drug with ac- itic acid. The following is his outlined methods-- Place in a bottle 10 grams of the powdered drug with 100 cece Of acetic acid, and shake frequently and con- tinously during 12 hours. Filter the solution and wash the residue with cold water until the wasjings are near- ly tastehess. lvaporate to dryness in a shallow dish, While warm add 6 cece Of a mixture of strong alcohol afd solution of armonia (10%) equal parts, rub to a unifm thick syrup with a rubben-tipped glass rod. Transfer to a separator, add 1 «a.C. of ether and 45 c.c. of chloroform, wash the capsuli with 6 c.c. of armonia 4) alcohol in three or four successive portions, shake 5 minutes, let stand for an hour or longer to separate. Filter the ethereal solution through a small dry fil- ter, which is to be afterwards washed with a mixture of equal parts of chloroform and ether. Finally distill of the ether-chloroform, and determine alkaloids by alkalimetry. 387. By the following procudure, very fair resu may be obtained in somewhat shorter time. Macerate 5 mm gms. of nus vomica in the finest practicable powder, for two hours with a mixture of 40% acitic acid 5 c.c. and 5 C.Ce of a solttion of sodiem chlotide. Add 90 cece of 50% alcohol, macerate with frequent or constant shaking for 10 hours. Take 50 coc. of the clear liquid formthe assay. Evapoate nearly to dryness on the water bath, transfer to a sudtable vial by aid of a smallamount of dilute alcohol containing 10% ammonia. Make sure that the ammonia is in excess and shake out with ether-chloréform (8-L) about 20 cece, and then with 2 or 3 portions of 15 cece ether, to obtain an a kaloid pure enough to weigh. Better however titrate with standard acid. G _— cr wa ~~ 388. Dragendorff's Method:-- (114) is efficient though it consumes a good deal of time -- exhaust 19 gms. of the finely powdered drug by boiling with three successive portions (159) cece of distilled water con- taining 10 drops sulphuric acid to each portion. After each boiling strain and press the residue. The mace should be nearly free from bitterness. lHvapor <7 Vv mixed Nt aad to the consistency of honey, ettlied é e the nearly having neutralized with magnesia. To the fluid ada 21/2 times its volume of 90% alcohol, heat to boiling, filter while hot alcohol and wash the res- iduxe thoroughly with hot alcohol of 60% strength. Distill off the spirit, add some subphuric acid, filter, Wash repeatedly with henzol to remove fatty and waxy i u ° matter, finally add ammonia in excess and shake out with several successive portions of 25 cece shloroform, evap- orate the chloroform 6d to obtain an alkaloidal residue =] i Which may be weished then titrated with acid. 589. yuibb's Method:-(115) A fair sample o is ground fine enough to pass through a # 9 siev grams of the powder are exhausted by cold percol oe percent acetic acid. The drv residue obtained fation of the solution to dryness,is treated in pel 10 ¢.C. of a mixture of two Betuies of 9I p alcohol,one volume of I0 percent ammonia and one of water . Move a stirrer over the smooth surface extract for I5 minutesi-then pour the contents o sule into a separator of I50 c.c. more of the am mixture. Now add to the liquid in the separator 40 of a mixture of equal and 96 percent ether. - then allow to ete measure the a. ether solutio hot water bath,so boiled off by the volumes and 99 cent chil Shake vigorous]; for five separate, When the separation dark upper straun,draw off the n into a tared flaskand immers that the chloroform ether time another washing ready. Y) P Y° VW . ana a is 7 may Pa . ae i} T ne f ruil: i y ana IG + ioyY ra +b } at 2 Y) c ee ‘ 4 < snow) ct Cc} tas arr + ard oe 7 2) or the | f th an- moni G40 rou Form C into a Meanwhile uld 40 c.ce more of the chioroform ether solution sho have been added to the contents of the separator,and the shak- ing etc.,repeated as The id la A third washing may follow if required. rt. mae Gar e ae) TN to Laver ic found TwGh. Y ’ 1 > , 2 ; ’ 1 a 7 3 s tgs a7 y 1 ‘ 4 y 4 1 4 } 7 t . * 2 ls 4 > . , . , ‘7 , * , ' ° 7 ad . , cd 7 4 7 = « . ma e 7 ks | = vad ‘ 7) E ” 7 = ; le { we ae ae ryt ar ; ; , af sy \ . : = t & gr aTorn {7 S } 1 ‘i e “lig "27 4.1 4 » iad 59 { ats oA Bs : =< of the emtls pes may be ignored.Finally add to the tare flask containg the total chlioroform-ether extract,IO c.c. -I-I10 sulphuric acid,rinse the sides of the flask wit} this and warm the flask bv emersion in a water bath Tha phe ea all the soluble alkaloids are dissolved. Add 20 c.c. of hot water and JO drops of logwood indicator and observe the color by transmitted lipht and match it by ansinilar quanity of liquid in another Finak: Then drop in I-IO N. caustic potash from another bure@éte until the color & changes to a slight pink tint. The tint should be very distinct when observed bv reflected lirht. Th umber c.c. used subtracted from the nttmber c.c. acid started with,ciwve the number c.c.e acid saturated by the alkaloids: and the number times the mean of the moheacular weights (0.0354 pl, 0.0394) plus 2) equals ots shed ee the weight of the mixe ed alkaloids obtained from To grams of nux vomica, the strychnine and brucine being assumed to be present in equal proportions. Then as I0 is to bhe product from I0, TOO to the Y) ercent?,of mixed alkaloids 390. Prescott & Gordin.(II6) Method:- The acidulate ] t the drics ovtaine water solution of the tota alkaloids ¢ eZ by any method of extraction, is made up to a aefinite vol- ume,say I00O ¢.c. If four grams have been taken,the 25c.c. Y e drug,end will be sufficien = to “+ - “Ss a Ba Z as will representone cram of tr for the acid. volume is run from e burette into a 100 ¢.c. flask in which have been placed 20c.c. of deci- \ eC. normal iodine solution, and 2e.c. dilute hydrochloric acic when the amount of iodine have been consumed by the total alkaloids in that one gram of nux vomica is reached as before described. The multiply this amount by 47.6,which is equal to I00 times the mean factor of strychnine anc at brucine,and the percentage of total alkaloids is obteinec. DERTIMINATION OF SSRYCHNINE. / 391. Assavs of nux vomica in detail require the qu ity of strychnine and brucine respe ctively in the tot 7 alkaloids. Any of the following are in neral wse. 392. Keller's Method (II7) For cdetermination of strvchnine jc pe y} aps the simp ar Coan Tesoral. TO ore] i the purified alkaloidal residue in 10 c.c. dilude sulphur- ia acid, {Io ) )yadd TeeCe nitric acid (sp. gr. 1.42) sl ix welleand set aside for twomhours, The add 40 crams chlor- oforn ,40 srams ether,and 10 c.c. of a 10 percent. of =) ge ammonia. Shake for several minutes ,put into a flask 40 prams of the etherial solution,and distl off the solvent, dry at 95 to 100 deprees C. and weigh. The distillation should be discontinued when the crystallization of the styvchnine begins,and the remainder of the solvent drive: off by air current. The purity of the strychni: must be established by dissolving a portion in concentrat sulphuric acid and adding 4& small crys&al of potassium nitrate which should not produce any red color 393. The assay process for nux vomica may obviously he simplified (strvehnin alone determined) by diss ing the whole of the unweighed alkaloidal residue obtained by any of the above assay processesgand representing 2.5 crams of drugs,in dilute sulphuric acid,and treatin; 7 % . _ ) above. Observe,however,that the residue so treated shoul be pure pita to a tolerablv blear solutianiry he dilute acid. Dt Mec, arv the residue must he purit ie OV aLtsst ¥ ing in acid w “ae h the aid of heat.filterins na shaki ; Sné Fa out with ether and chloroform. [t is better to extract all of the strychnine at last by the s successive nortions of solvent than to follow } 4 } Ti. 4 1, eo} A s ' - , is ve > 4 method,which assumes that the whole of the alkaloid has been abstracted by a single washing,and Which invole dan- er of loss of volotile solvent during the required le m Ss a ° a] : Piltration and weirhin e ~ ~ oO . ~ ry L 2 predtoccassionas SnNaking, 3 _Lta or ae at. i 4 nent liauvid with more picric acid 1 Liaqu ! An ~ s T) ont and add more if necessarv. Decant - “ o ‘ sw = + 7 = . ly as possible and wash the perci = : decantation with water. Dry ina , ang we L Bn ° es m 2 ig a a oé + I 595. Treat the crvstals with as adopted by the British Pi (Having brought the alkaloid extract of nux vomica into s by the shaking out process), 5 portions (10 C.C.each) of taining 3% sulphuric acid ution to 175 c.c. ,add 25 c. of potassium ferrocyvanide, shak half an hour in a stoppered : < vy) cry cody’ ~M | w J nNux € decinormal aL neu! 0956,keep at 60 der TN idea he Ferrocva nide Forma to a ng one twenty vornica th 1 sulphuric aci c te cir es to 1 sie es mat e pur te er a Set hal (iLL € A LO 4+ «5 + 20,0 mor ¢ cino st su Y ant 2 md + wr a > LIME €S A Aer - 4 t < nates. " nour > mo ek 8) Te 4. a We « ‘ Ged c/ , _ ra | Mie t atad & ° Cc . > 4 a t«a “ ‘ wl e Co PI WAC Tt = { 7 v YC Cr i 23 c ecia a3 35 ee JGR ete 1a7 a ies > mMiete ii} = Py +n ¢ nertor a aaa [Of O29 IO 397. H. M. Gordin & A. 3. Prescott, in the course of their researches on the estimation of alkaloids as perioc= dides, found that, along with modifications of Dunstan & Shorts method of assay, the periodide method afforded @ very convenient way of estimat ing the amount of the two alkaloids separate ly in nux-vomica; The amount of total alkaloid having been ascertained in an acidulated solu- +} tion obtained from nux-vomica,in a suitable way by the periodide methdd, the process is further conducted as fol- lowsi:-- 5O c.c. of the acidulated solution, representing 2 grams of nux- ~vomica, is run from the burette into an Erlenmeyer flask of the capacity of about 300 c.c.; 1 ofa 2% solution of sulphuric acid is added, f ferrocyanite, is run in. The flask is stoppered contents are shaken continuously for about half Now, filter, wash the precipitate repeatedly wit containing 1% of sulphuric acid, let a few drops ‘of the filtrate diluted with a little water, have no bitter taste; | The filter is then pierced and the precipitate rinsed with the wash bottle into a 100 c.c. flask. Then add 20 Cee. of.a 5% solution of zine sulphate and keep the flask on a boiling water bath for about 15 minutes. The zinc sulphate decomposes the strychnine ferrocyanide, strych- nine sulphate enters into oleh and zine fe ‘rrocyanide is precipitated, the brucine phosphate having been ° away by the previous treatment. The flask Pa then compaete ly cooled and water enough added to make 100 c.c.:=-- of this, 50 c.c., representing one gm. of the nux vomica but deprived of brucine, are then filtered off, run from <¢ burette into a 100 c.c. flask containing 20 c.c. decinor- mal hydrochloric acid. The amount of iodine in excess is then ascertained by means of a standard solution of sodiu thiosulphate and the amount consumed thus determined | subtracting from the original quantity employed and, by multiplying the amount of consumed icdine by t MEiRinining 43.9, gives the percent. of stryc the mixed alkaloids. the factor is 47.845; for alone, it is 51.7 598. Galenical preparations, Assay of:- Measure 5 c.c. of the fluid extract or 25 c.c. of the tincture into a cap- sule. Add one c.c. dilute sulphuric acid 10% and add 10 CeCe Of water. Evaporate to expel alcohol, adding, if nec- essary, more water. Pour the watery solution, measuring about 10 c.c., into a 2 oz. vial having a good lip, rinse the dish with ether and a few drops of water and add the rinsings to the contents of the vial, wash the acid fluid with several successive portions of ether, using for the last washing, a mixture of chloroform 1 volume, and ether 5 volumes. Having decanted this, add ammonia to strong alkaline reaction and wash out the alkaloids with 4 success ive portions (15, 10, 10, and 10 c.c.) of the same mixture / of chloroform and ether. Bring the ethereal solution to a volume of 50 c, gCe. evaporate 25 c.c. to determine total alkaloid. in the : P vu} i inde fter evaporation determine strychnine as by (3838 5°5 (3 96). pene . 399. For solid e pregks . the method of H. seckurt's is commonly followed. 120 me” extract (2 grams) is om ved in a mixture of 5 c.c. water, 10 c.c. of alcohol and 5 c.c. of water of ammonia and shaken out with several successive portions of chloroform or a mixture of chloro- form and ether. It is as well to dissolve the extract as above and make up a volume of 25 C.C. and, of this, take for the assay two portions, each of 5 c.c.. in one of which, total alkaloids are determined, in the other, strych nine, by the method of Keller (392). rons 2 n] 2 } Ve 400. Nagelvoort (127 directs to weigh in a small flas a quantity of extracts approximating one gram. In case some of the extract adheres to the neck of the flask, no attention need be paid to this. Put into the flask, 5 c.c. of 10% sulphuric acid, cover the flask with a small beake- poy er inverted and warm on the sand bath until the extract all dissolved or reduced to a homogeneous semi Wash the acid solution three times with alcohol Then render alkaline with ammonia and wash out This method is preferable to the preceding. may advantageously make up the acid solution take aliquot parts for the assay, 2s suggeste paragraph. 401. Method of J. U. Lloyd:- Into ag 1) 5 c.c. fluid extract nux vomica and 10 c.c. of chloroform, then add 8 grams Lloyd's Mixture (equal amounts of dry fer- ric hydrate and sodium bicarbonate, mixed), stir together and add Glucose mixture (equal measures of glucose We ter), from 2 to 4 c.c. , enough tog form a pulp. Sti briskly and decant the chloroform into a beaker-glass then successively wash the magma with two portions of chlo- roform, each 10 c.c., decanting each into the beaker. Should the magma adhere to the sides of the graduate, abov the stirrer, scrape it down occasionally by means of the spatula on side of stirrer. Evaporate the chloroform, pou upon the residue 6 c.c. dilute (1 to 49, by measure), sule- phuric acid, warm gently and filter through a small paper into a four or eight ounce globular separatory funnel. Wash the residue in the beaker twice, with di luted acid , 4 c.c.,each timestirring the undissolved back with acid, means of glass rod,and filter through aforenamed filter into the first acid solution. Make the mixed acid solu- tions alkaline with ammonia and add 10 c.c. chloroform. Rotate (not shake) a moment, then adstract the underlying chloroform into a tared dish. Repeat the washing with two successive portions, each of 10 c.c. chloroform, tae arcck ing them into the vessel with the first portion. Evaporate the chloroform, bringing the residue the constant weight in dry oven; multiply its weight,expressed in grams, by 20 The result will be the alkaloidal percentage in the fluid extraees. 402. Nux vomica contains from 2 to 3.25 percent of al- kaloids of which about 42 percent is strychnine. A fiuid extract, however, cannot be easily made to contain more than 1.5 percent of total alkaloids, and this standard is the one now accepted by manufacturers houses. Ignatia con tains about the same quantity of total alkaloid as nux von- ica, but a larger proportion of strychnine. co OY 403. OPIUM.----- Gum opium, the concrete milky exue- dation obtained by incising the green capsules of Papaver Somniferum, occurs in commerce in the regular subglobular lumps weighing from 4 oz. to 2 lbs They are enveloped in remnants of poppy leaves and with chaffy fruits of a spec- ies of sumac adhering; when fresh, it is plastic, breaking or tearing apart, showing an irregular, chestnut-brown sur- face, shining when rubbed; odor peculiar, narcotic; taste bitter. When examined with a pocket lens, it is seen to be composed of yellowish, agglutinated tears. The valve of xk the gum is only determined by assay. It should contain, in the moist condition, not less than 9% of crystallized mor- phine. When well dried at a temperature of 105 degrees C., it should yield about 55 to 60.percent. extractive, Powder- ed opium (U. S. P) should contain not less than 13 to 15 percent. got morphine. When the powder is extracted with about 10% of ether, the ether solution rejected and sugar of milk added fo the residue to restore it to its volume (original), it forms denarcotized opium (Opium deodoratum U. S. P. 404. Adulteration-- To increase the weight, various articles are used, such as sand, clay scrapings of poppy capsules, and various mucilaginous albumin 1i0usS and sacchare- ine matters. Lead bullets are often used as well. 405. Opium is a mixture of sixteen or eighteen dif- ferent alkaloids, with meconic acid. coloring matters and various inert substances, The principal constituents are the following alkaloids:-- Morphine, papaverine, meconidine pseudomorphine, codeine, laudanine and oxynarcotine; these are in combination with meconiec and thebolactic acids. 406. Of the opium alkaloids, morphine is the most dant and by far the most important , and an assay of the drug or of its galenical preparations calls usually for a determination of this alkaloid alone. Morphine exists in opium in the form of a salt readily soluble in water, which medium mm then is better than alcohol, for exhausting this principle. The narcotine is mostly left behind in the a- queous extraction of the opium, although it is more cer- tainly excluded by first treating the drug with ether. Otherwise, the separation is made either by precipitating the morphine with ammonia in the presence of ether, which fold. narcotine in solution, or else by the use oflime or barvta. ch hold in solution morphine but render st pers which, Le narcotine, - y ender still LS aod 407. Morphine (the alkaloid) is nearly insoluble i: cold water. It requires for solution, 500 parts of boi water, 100 parts of cold or 36 parts of boiling 90% al hol, 60 parts of cooled or 13 parts of recite! absolut alcohol. When crystallized, it requires over 6000 parts of ether, nearly 9000 of benzol and 4400 of chloroform to dissolve it, but if the solvent is applied at the moment that the alkaloid is set free by an alkali, it requires ether about 1000 parts, benzoi 2000 parts and chloroform 860 parts. Hence the alkaléid may be practically removed from an aqueous solution by shaking with ether immediate] after it is added, but much of it will in a short ti erystallize out of ethereal solution. In assay work, enly solventsbuitable for a shaking out proces acetic ether, amylic alcohol or (léss obje etionable in odor and toxic effect on the operator) icobusylic alcohol. Mixtures of one or other of these with chloroform are som times employed; chloroform alone abstracts the alkaloid very imperfectly. hg BE peer on of @pium Alkaloids:- scheme for the separation of the prin of opium, may contain sugge stio ys useful to aqueous solution containing narcotine, papaverine, narceing thebaine, codeine and morphine, add a concentrated salution of sodium acetate and let stand 24 hours. Narcotine and papaverine are precipitated. Dissolve the washe tate in dilute hydrochloric acid, and dilute its weight, add potaddium ferrocyanide to precip 24 hours) papaverine. From the filtrate, narcotir cipitated by neutralizing with ammonia. Comcent: solution from which marcotine and papaverine have “bee moved and let stand 24 hours. Narceine will separate Filter and add sodium salicylate. Acidulate the fil with hydrochloric acid and shake out repeatedly wit roform to remove remaining salicylic acid, narceine ; thebaine. Drive off dissolved chloroform by a gent] and add potassium sulphocyanite to precipitate codei After 24 hours, filter and add to the filtrate amm tah “to precipitate morphine. 409, Sampling opium for Assay:- Where assay had to be made of a case of opium, some systematic method must be adopted for sampling. Dr. Squibb directs!- From every fifth larger lump and every tenth smaller one, cut a cone shaped piece, the apex of the cone to be at the center of the lump. From each cone, take off a slice which shall represent in due proportion, the moist centre and the drier exterior portion. Collect these slices of approximately equal weight into a mass, working rapidly so as to avoid evaporation of moisture. Roll into a cylinder, Repeat the process six times to ea a perfectly caer poly Mass, 4 Pa fe fe quantity tarch being user olling out if th Spium-is motst. ui sticky. ‘Tws SEA $9E nb , eace a? 9 nee q Two portions, each representing 10 grams lowance being made for the starch that |! then weighed off. One of these is flatter disc and dried at 100 degrees C. to con determine moisture. The other is to 1 410. The Paris Society of Pharmacy the following method for the valuation 15 grams of the opium to be tested, are with 9 grams calcium hydrate, 150 c.c. ed with constant trituration and the mixture agitated for 1/2 hour. The mixture is then filter and exactly 100 c.c. of the filtrate glass-stoppered bottle. 20 C.Ce @1 dissolving 6 grams of ammonit is allowed to repose ae 2 hours. The ether ed, replaced by a fresh portion and, after r recipitate of r jon, again decanted. The p it O ly collected upon a smoot ie filter, washed with of cold distilled water, dried and weighed. minus the ie of eee z. See al ka Loid and ail. eos Assay I g = a5 dered opium are digested with 100 grams of water for 12 hours, with frequent shaking, > 1 acidulated by 1 of 2 drops of dilute sulphuric already acid to litmus paper. The whole is a P re) a : ae “ psn et never ea TAA) ser eat Ts rae tared filter, the residue on filter washed with wate! ce 150 grams filtrate, which may be designated as Pera No. 1. The residue pon filter is carefully returned flask, 50 grams of water added, and in same manner 150 grams are abtained=."Wo. 2". The residue on filter i percolated to the extent of about 20 grams more, percolate #5, which is used for rinsing the vessels in su operations. Percolate No. 2 is evaporated ina Sule to about 20 or 30 grams, tnen No. l added, and evaporation continued until the whole is reduced to about 10 grams, not less and not much more. ; is transferred to a flask, rinsing th the weight of the whole not less te grams. Then half its weight of alcoho] is added to the solution « the mixture is ether of sp. gr. 0.725 are added and Lo le Shaken, Then 4 gms. solution of ammonia of sp a bseq + & ~ e are added, the mixture shaken and allowed to stand over night, the ether layer is decanted as closely as possib! observing that no eryst “als of morphine shall be carried over with it, and 15 grams AS bes ether are poured into the flask which is Tange’ SO as to cause a thorough rinsing of the sides of the flask, and then decanted as before; a third portion of Siictis 15 grams is used in the same WAY 412. The crystallized morphine is collected on a dor ble filter with the usual precautions and washed, observ! that the filtrate and washings shall not exceed 40 c.c. KM The morphine is then dried to constant weight at 100 degrese C. and then weighed, using the outer filter to coun poise the inner. 4. 413. About 0.1 gram of the morphine thus obtain now agitated with 10 c.c. of lime water in a test tube. If the morphine dissolves to a solution which is nearly or quite transparent, and from which no weighable precipitate g@ fs 1+ = settles within one hour, then the contents of the are accepted as being practically pure morphine 0.5 gram of the powder is agitated with 50 ee solution filtered through a double tared filte washed with 3 to 5 ec.c. of the rinsings of the which solution was effected, then washdwith 5 c.c water and dried to constant weight. tained, is calculated for the whole q y phine obtained and is deducted from the latter 414, The method of E. Dieterich (125) ag adopted by the German Pharmacopoeia, is as follows:= Triturate 6 crams of finely powdered opium in a mortar carefully with of water, dilute and wash the mass with water into a c Suitable tared flask, and add enough water to make the mix- ture weigh 54 grams. Macerate chigstae frequent stirring during 1 hour and then filter through a liated filter of a diam- eter of 10 cm. Take 42 grams of the filtrate, = with it, 2tC«e@.: of W/1 ammonia, without strong agitation , and pass it at once through a ready prepared pldated filter of lO cm. diameter,; 36 grams of the filtrate, representing 4 ems. of opium, are mixed ina tared Erlenmeyer flask, by circular rotation with 10 grams of ether: next, C of normal ammonia are added, the swinging or rots tion continued until the liquid has become clear the flask is corked and set aside. After sta at most, 5 hours, the ether layer is first t: complete ly as possible, upon a plain filter of 8 cm. diame eter; then 10 c.c. more of ether are added to the contents of the flask, the whole again rotated and the ether layer again passed through the filter. When this has all run Ly Seep the aqueous solution is poured in without having regard for the crystals which adhere to the walls of the flask, Finally, the latter as well as the filter are wash- ed with 2 successive portions of 5 c.c. each of water saturated with ether. After the flask and filter have been allowed to drain well, both are dried at lOO degrees Cy the SB. Sute quantity of matter retained by the filter trans- ferred to the flask and the drying continued to constant weight. 41286 eda Mare et Modification of Dieterich's Method of Assay. i. Prof. Cornwall, at the request of Dr. Wm. Ke Newton, the New Jersey Dairy Commissioner, has made a series of investigations for the purpose of determining the value of several of the assay pwocesses proposed at tha time. The principal object was to ascertain that met which being at the kimme same time the most convenient ar least liable to error on the part of the analyst, would give accurately the proportion of morphine, when the fell within a reasonable limit above or Sarl? Leg standard, rather than to seek method whi most accurately the percent. of morphine, wha amount. The various methods of Squibb, were tried and the author concluded by r following modification of Dieterich's me most satisfactory results:= Place 6 gms. beaker, edd 60 c.c. water, stir écéasdonaliy all theluwmps).over night for 12 hours. Filter inte uated cylinder, wash the residue on the filter until the + = t ag a DY 2D filtrate and washings amount to 75 c.c. and set this aside. Carefully return the residue to the f 11 witl 20 c.c. water, let stand 10 minutes a same filter; repeat the operation twi with 12 c.c. water, finally pressing rod. Evaporate the last three washi in. in diameter on water bath, below th iling When down to 15 c.c., add the ist. st rong extract, rinsins the cylinder with a little water and evaporate the whole extract to exactly 50 c.c., including the water necessary to rinse the solution into the measuring flask Add*s ¢.C. normal ammonia and at once filter as directed process. Of this 4 gms. of opium, add 3 to 14 ¢ the flask nd then add 4 c.c is e I ce. of ether, mix by rotating oa ¢ 7 mae oo Atswantarn norma. ammonia as alirected © fod a | rm i in Dieter ich process, and outlined in ts | 1 @, Ww %G n e cL 5 say a i r e Cc y L Y @ ce Ss this process. 416. Prof. A. Fluckiger estimates morphine as follows &§ grms. powdered opium are placed in a pliated filter l em. in diameter, the funnel being slightly tapered in orde to bring the powder to the bottom and the whole dried at lOO degrees C, After half hour, 2a mixture of 100 c.c. chilo- roform and 10% c.c. ether is poured upon the powder, the an funnel being covered and tapped a number of times; then, 10 c.c. chloroform additional are poured on. After the liquid has drained off, the filter is spread open and the powder dried at a slightly elevated temperature. The powe- der is then shaken with 80 c.c. water to which 4: ° ed 0.2 gm. ammonium oxalate to separate the cal and filtered after 2 hours. 42.5 gems. of the fil treated in a small flask with 7.5 c.c. alcohol 15 c.c. ether and 1 c.c. ammonia (sp. ger. 0.96). hours of occasicnal shaking, the contants of the poured upon 2 pliated filters, one inside of the 10 cm. in diameter, the flas! cc being rinsed with a ‘ water or an aqueous solution of morphine aaa poured on the filters. Th are dmed at slight1 ed temperature and at las is then transferred to the 100 degrees C. and the whole he The morphine obtained represents 1/2 the opiu + M2 un 417. Method of J. Howard Wainwright (128 Labaratory, attached to Custom House. (This fers @niy in some details from that of Dr. Squil into a 4 02. wide-mouthed bottle, 10 grams « with 100 c.c. of boi ling water. Cork securely e ® - am stand, with frequent’sShakings, for 12 to 24 the clear liquid upon a filter of convenient ect the filtrate in a beaker. To c residue, CwOs more boiling water. Agitate again mass to the filter with the aid of a lit Drain well on the filter, wash with a ve applied drop by drop, around the edges o1 418. Return the residue to the bottl with 50 c.c. hot water. Pour again upon collect the filtrate in an evaporating di the residue with hot water unt ce ete Evaporate the filtrate amd when reduced add to it the first filtrate, a little < whole is reduced to a volume of 20 c.c. Tran: aid of the least possible quantity of water Erlenmeyer flask and, when cool, add 10 c.c. strong hol (observe whether this produces any tendency to. ct cae st QO & © te ro i) r ‘Ty ~ fe a precipitate. If so, add 10 c.c. more of alcohol, an hour, filter, reduce filtrate and washings once 7 20 C.C. and again add 10 c.c. ether equal to that of the mixture, cork and Immediately add 4 c.c. (better 3 c.c.) of 109 again and shake until crystals of morphine begi arate. Set aside in a cod] place or else shake ly half an hour or more. (The best plan is mechanicai shaker at least 6 hours). 419. When the morphine is completely prec cant the ether upon a pair of mutually c : Add to the contents of the flask, 20 c.c. more Shake once, let separate and decant this throug which is to be then washed with a little ethe ‘ drop by drop, to its edges. Remove the last ther from the surface of the heavier liquid, a Strip of filter paper. 420. When the ether has drained th rougn p our on the filter the hydro-alcoholic solut Le tals of morphine Wash RE tal 3k ~ 4 Api 2S Cc ry st , Ls Tsk’ (and be jae wa 4a of portions Hf the 1 j qu i Ae When all the fluid has passed flask (and beaker) ; hom EY - rated aqueous solution of ¥ crystals on the Filter wit tilled water until this c e filter thoroughly, fold, - ly dry at 100 degrees C to any crystais have adhered dried and weighed. 421. The morphine thus If dried at 100 C, it retains deprive it wholly of this, n hour at 110 C. The better si- due at about 60 degrees C. and weigh the crude Which is afterwards to be dissolved in volumet chloric or sulphuric acid and titrated } ri soda solution, 1 gis ng cochineal as i of dectnormal acid indicates 30.23 Mes phine which is unin reported in 92 4 or ac aM rte > Te opis Tec or 28.44 mg. of anhydrous alkaloid. form but » of water and, after two hours Shaking, filters and introduces i filtrate, supposed to represent 4 grams of the oviur Strong alcohol, 20 c.c. ether and 1 ec.c. lt a t 9 C 4 Jyo arom ne? ig Tye oA Gc ee es’. _ Nga 2 os = “Toe oh > proceeds otherwise as in Fluckiger's method. 7 “ao - : ye re ps > 4 = , ( ) 423, Hager's lime process as modified bv seckurts ‘ + fol 15 AS lowsi:- Macerate 8 grams of powdered pium for half an hour with 79 c.c. of water in a well Stoppered flask, add 3 grams of freshly slaked lime and, after shakings for one hour, filter off 51.5 c.c. 9 grams of opium. Pour upon this so as tc ] CeCe. Of a mixture of 1 volume aleohol. a which mixture has been Saturated with o 11 & Saturated solution of ammonium chloride and Gusly. After 6 to 8 hours, pour off the et a filter moistened with ether, shake the mi 10 cece ether~alco hol, transfer the etherea the filter, and after it has passed through, pec | aqueous liquid together with the erm ystals of morphine; fash flask and crystals with a morphine-saturated solution of equal parts ether~alcohol and water, dissolve in boil- ing 90% alcohol, filter from the tindissolved calcium meco ate, to the filtrate » to the filtrate, edd 25 e.c. of decinormal hydrochloric acid and titrate back with centi- si ; Sie eee pee normal soda, using cochineal ag indicator 424. Method of aqueous solution of of opium, mix this water to make 85 occasionally. at mouth, fitted with an accurate. of the filtered fluid, add of ether and 2 grams ammoni tervals during half an hour, ce Fb pe ~ Hy fete bee £9 trate with 8 2 UtL > D ~ —) oO to =) lato — ma) + PB e > 1 09 A w Ota + =) qu) % e rc >a * 2) ©, Cy ¢ O Pe) et e of a powdered 1.8 gm. of mixture to MO "22 CeCe acid just (about 1 c.c.),warm the solution to te we to subside,and filter. Wash the re washings, add dilute ammonia t and concentrate to 6 0o ether and ammonia in slight excess, r : Lig hould be a distinct odor of amnoni loa mY Oe 4 . £ ” 4 vr 1 i = Tl a pair Os il ua t morphinated water, 2 ae - ry + 1 ++ finally, titrate wit “i > a | 49 Wa+) ~ < ( L pe HO e etnoad pi Je Pe reer ry es |. = 1 = . wr 3 + a a ~ + opium a short time with 150 c.c. wat By, « 729+ aw ana’ ha jee a3 baryta. ilter and boil the residue P oa S apen + 7 : _ ay | 2 i wn hy quantities of water until filtrate avoided and the f t e.¢c,.” Pass ‘through ‘t) — to precipitate the barium. Evaporat bath, to dryness. Moisten the residi transfer to Erlenmeyer flask ay with absolute alc ilreay “DPStiILTL off’ thé*alcohol, containing some ammonia, and alli ll with a glass rod, collect the mor ter, dry at 40 degrees C and treat form. The product may ? ed) and titrated with standard acid. T -~ ef 4 SG fe Te hLoeil J +l, um salicylate, thi ; red: the salicvl Yea, vLlS sALICY constituents of opium wh @,; Nis process as aoaders d opium are car ted eva o gms. water, Wate CQ cr Fh jo er) 44 ammonia are added, 10 minutes. The morphi small filter, the flask ings being poured upon \ 4 je 4. } 4286 ‘oo= After test the authors a er the or one hour and fi - of the sodium chloride and treat the residue further with sox a drop gives no reaction with Froehde' Evaporate the mixed filtrates to dryness on a water bat } > r - - 7 " extract tne residue with boiling absolute L (300-350 c.c.) until the fluid ceases t@ give a reaction with mehahds "s reagent. Evaporate o Wale cS (cies of (a every. «ahi: cee 24 hours. Collect filter, wash with water washings are col the dried morphine on the evaporating a few drops, c: ric acid and adding soda solu = ion, no : »btaine The morphine is then dried at 100 degrees and weighed, ( 2 1489. Assay by periodide Method of Prescott and Gordin 135);... One gram of the opium in very wde } put into a small mortar which can be well cov: i with admissio of a small pestle. (a4 oz. screw top n rounded bottom answers verv well, the rt ed to admit a pestle). A mixture is me ) F r er solution of ammonia, 5 cec. alcohol "orm J 2 * sn 4 . } and 20 cec. ether. The opium is ribbed C.c ra) } - ms -w4y . t n ys nA SC of this mixture to make a uniform paste, dish is put t hours being cent noved from time + A ake & 5) 6H ss v- 7 . ! “ 4 ‘AS 4 me sib / wi dat F - Pe - ie | y- > > _ : Pd 2 5 to time: 15 grams of well dried and finel; NV da i chloride is now added and carefully mixed with the mass, >, when | ) if erad oref a in: ve ary ~ & S Cc Ord a a Leman | 18 + —{ orf S isi J n @ L0 sy iA GD 11€C o» Yr Cn 44 yt - i * Cay a rr bed S Tos [oJ 2 ce $1 ral ~ => ed } a5 [7 ¥? 2 oi ¢ > by a) SS, of “yo Ka tas = o% a tT 1 4 a =a ° be er | > a) me ou - is a] Sot 2 ES, * RR oi > + J — 1 = is rn ce produc Jerre? VG } , Bs ‘ae mS .e 2 C& rec Ae ca Con to & , I rn r mn or aA CO 09 o- = © ir ri © - Cr+ Po ee) ce eae jt , ‘ei Neo 0 a ¢@ oH a OS fal mao 8) So >) c ‘ = ei eS TaN + ~ = or « can) mM - mi as ake <) LheES J ar “: : at Pepe e ~ SO | C Qe eino? 10a; a ant | f A r JiLL 4._\ Cu \o Al inc BSOLUTLON corresponas A it 433-6 William R e Lan Nar es sample of powdered 0}; noticed, after having concentrat bDrourht. it Tbe t that the additio a pronounced f after the additi nat diminish and, aed * LUM ac cerada oO this in liminary 8) gr ti ons until the washings pass bi $5 Cec. of water, evaporates of ataoac £n TA — ,< Oe ok oe a ee trates fo 1% GMe, AS orTiciall alcoho accord thoug bean ef one he final Opium (160 c.c.) is be evaporat poured in a thin stream with constant of cold water, the dish well rinsed, ’ the mixture, then with water suffi- exactly 150 c.c.e Tet the mixture evaporate 100 c.c. of the filtrate nmever flask and pro- ve ask As an alternative pro- not, * o Z rn rn mA incture to 30 c.c. and occas etnereal routine as ABBAX one ae lux conde Ons oO a i] ® L or °F Pest ip 4 T 4 { & oe } i + ae | rl Oc t. @ aes - ¢ nd @ n A, 5 i res - = bes & . ls 4 ~ 4 be > @ 7 > 4 it “ ; &9 @ 3] © © ® 1 “ a2 f @ ¢ 7 Ln | Ww ae e 7] a 2S Ad oO a) a m apm ort Ay oC ; O ® ) @ act + ar ‘ fh e = ee rpidine m wv e - Oo rt wo a + Or 4 ce BW pam ~~ tw Ve +> se | S++ @ A bL _ © = ~- ] fy ®O & Lae cg .2Q0 etieE Cc “4 @ ra Qe ct © S %, Co WM @ i = = — (wie ony en © my O ws 4 O Ssary ECE tv bse “oposed me cams of th od t ‘a’ "FP > 4 4. nya 1) + l or 2} a aisti AMA AIR =e i) annem 17+ x Ane “ 4 . . 4 ae 7 i , « 5 = +3 4 a : - wr oT 6) 4 as - 7 7 Bt Fn fe I] | ta 3 g ° v4 "7 ) + Sin fi er i Du e i earl 2 - t& wo UU z ® runn . wr) url t+ pl $a 8 . awn, W 3 e “a tes 7 a4 ot Syl ae 2 we Yé 3) @ i = & | H e , 1+ & L. | a . 4 é = ww Lid. ve. ro] ! - 5 ~ : ; ALO LELe 4 wD o) aAannin LAalIlrlin yWA+ SAtMnes } La . i ae | ) => 2 cy excess f+ *s 1+ wa da Ad ey ie inte rk © Ua eet ands iw s * > rad ith j } 4 4 a © rr) 4 : at- To > D S y + VA + =, | . - > . . and CnMrough this solut} Nn, carbonic an- ri I and, p h 3 SPANStGntdisremavertrageandfdtdad. Akaerxtitirs- ¥ Ya ggen 7 } » ad y "rc + a, ann i & a9) I @Cm¢ > ! i +” + ~~ ~ a > 4 o A bY - 30 Luti 7, Swe Wwe - J Av 1 OF] LS € LOOY 4 Be é m 1 e oy . } “ 7 i } mY } al e 4. we + 4 - 4 1 5 4 . Lv "roy > 4 vy 4 ; f a) 4 n+ 5 Cabl } ° Y ~ HN Ore c OTe) ) ae ALY } nthiy ; Ila Fr he I e ‘ ct t omer \ L i i tw tw axx Ps. 100 a6 e a T + + f <) - ? 1 J » Kremel (142) exhausts the drug, by hot renercola 462 3 tion with a mixture of chloroform and absolute alcohol, equal parts,agitates the solution with several successive portions of water acidulated with hydrochloric acid, filter the acid solution,renders alkaline with caustic potash, and shakes out with 3 successive portions of chloroform. He Peports a yield of 1.5 to 1.5 percent.of white alkaloid from veratrum aloum,in the form of white seales and mic- roscopic prisms. 7 465. Jervine, which is the most abundantalzaloiad T 1, = " . hk < 2 en oo yn : = although possibly not the most important, therapeutically, may be easily determined by taking advantare of the insol- ublility of its nitrate in a solution of potassium nitrate + a my { rz 2 . : ; The process (145) is carried out in the followinre manner!- re dissolve the emide alkaloid obtained from the « from one of its preparations in dilute acetic acid, filter the solution and add an equal volume of a saturated solu- tion of potassium nitrate. Set aside for twelve hour collect the Jervine nitrate ona pair of rmutuallv counter- _ i see Pry — 1% as . aoe . : poised filters,wash with solution of potassium nitrate and Finally with a little water, drain,press between blotting , — m "rc P im 7 = s % paper,dry at 75 to 80 degrees C. and weigh. Assuming thet the nitrate is an anhydrous salt of normal comnosition We snall not be far out of the wav of the weicht of the saltis al if we recon on 89nerceh kaloia 464. Assay of Galencial Preparations:-A fluid ex- tract may be assayed by (I3I) et. seq.,but it will be found difficult to obtain the whole of the alkaloid - ER is advisable after extractinr several times with a mixtur: of chloroform and ethe r,to employ pure chloroforn, ada iy y ‘ a little alcohol to prevent the formatior + at ,»ne same + Ime ad of an emulsion. If an emulsion should forn,resort to the saw-dust process. (159) ,wt ich may indeed he adonted in ef,although not with our usual confidencethat the . : , - , whole of the alkaloid will be extracted be evaporated to consistence of fluid extracts and then \ treated as above, Hxtracts are rarelu used but would be disolved i small amount of menstruum and treated as fluic extracts. A 65-6 H.W.Snow (144) after workings for some " ano th of time upon an assav process Por we ratrum nronoses the followinr:- xX Il5c.c. ofthe fluid’ wxrtratt' with 60c.c. tre we 4 is 4 L ‘ ws 8 Of alcoiol,containing about 6 c.c. of a saturater solutior of lead acetate,shake and allow to stand a few minutes. Filter through a drv filter,take 50 c.c. of the filtrate, equivalent to 10 e.c. of fluid extract,yremove exce of lead by hydrogen sulp! ide,evapoate to expell.the alcoho} add water and a little acetic acid to make up the volume. rr ‘ . , mr yD - mn 4 to JO c.c.,and titrate with Mayer's reazent(N-I-20) ,of which each ¢.ce will indicate about I5 millicrans of alkaloid. instead of estimating the Pte iad hy. Citent ion we may extract it with chloroform after ahGine an alkelo? but,as long as our knowledge of what is the real active i : Fs 1: 5 . eee ee : ca : * ; ae é princip] e of the arvg,sis so imperfect,the above is the best method. --3 Summary ;-- The choice of methods for individual drugs and preparations will vary a great deal with the oper- ators. What one chemist may deam a good method, anoth- er may think entirely worthless. I will give below the methods preferred by me in each drug in questions~-- In the assay of aconite and its preparations, I have found prolonged contract with alkali decomposes the alkaloid and the results always run low. For that reason the perforator method in my Opinion is utterly worthless. The sawdust method (159) yields the best results. The short assay process (71 and 72) also yields good results. No matter what the process of assay, after my finished product is completed, it should answer to Squibbs Physiologéal test (194, 195 ana 196). For Aloes I use method exactly as given in 202 with good results, The drugs Belladoma, Stramonzum and Hyoscyamus, I have classed all under one head, since they contain id~@w tical or nearly related alkaloids. The main thing to bear in mind is that we are dealing with alkaloids easi- ly destroyed or altered. Methods used for standardi- zarion must avoid the @ plication of heat, or long ac- tion of alkalies, strong acids, ete. Henbane contains such a smmll amount of alkaloid, that double quantity is generally employed. The method preferred above all others is Thomp- son's Sawdust Method (159) used on all three of the drugs. Such methods as Dr. Schwickerath's Q 2159 etc. are utterly useless. The Cantharidin from Cantharides is best separat ex by Nagelvoort's method. By continued use of it very close results may be obtained. The assay of Ciuchona may be accomplished by any one of several. I prefer the methods of Prollius li- quid by taking about four gms. of the drug, digesting with 100 c.c. of the modified Prollius fluid and then followingy the routine of (72 and 74). No few prefer the lime process ( 281), but the assay always is short, due to loss of alkaloid from the prolonged contact with the lime solution. Cocoa leaves are best assayed by the short assa process (76). This method gives good results and a Particularly pure alkaloid. Squibbs Kerosene method yéelds nearly as good re-~ sults, but is harder in manipulation. ow The Assay process which I prefer for Colchicum Seed or Root is same as given in (294). It yields peb. terresults and purer alkaloid than any other method. The precipitation with Mayer's reagent is used by no gmall number but in my hands do not give as good re- sults as with method above stated. Conium containing a volatile alkaloid can be sub= jected to heat without loss of active prinviples. The Prollius mixture yields goé@results. But any method at its best is far from satisfactory as thereis no satisfactory way of liberating aqueous solutions con- taining salts of coniine. fhe alkaloid seems to affect the indicator phénolphthalein, so that the alkalimetric process cannot be resprted to. Mayer's reagent pre- cipitates the alkaloid only in quite strong solutions and the precipitate runs through an ordinary filter, tH) so that good results cannot be obtained by this method. The method of (803) yields by far the best results. The Assay of Dightalis Leaves has been a problem af a great amount of discus ne Some claiming no chem ical means can determine the apeutic value of a sample of digitalis. Other claim the chemical assay the only correct way. Il have always followed Keller's chemical assay as given in (810). The assay of Elaterium is in its infancy. The method @f (321) is a process I have of determining the content of elaterin and yields fairly good results being a drug of little medical use, the assay process 1s nov as perfect as those of more extensive use. Ergot comes again under the uncertain class of physiological vs chemical method of assaye While l be- lieve in the physiological assay of ergot, my facili- ties compel me to use the chemical I always use (820). The assay of Gelsemium is best conducted by the process of (71) to (?8), the alternative of (72) being preferably followed. The alkaloid is always of a dark color and apparently of a complex composition. For tha reason i always use the alkalimetric titration rather than direct weighing. The titration with Mayer's Reagah; (882) also yields good results. Guarana and other drugs containing caffine are best assayed according to the method of Prof. J. W. Lloyd (168). The alkaloid is very feebly basic so that it cannot be determined by ,lkalimentry, at least with any of the indicators ordinarily employed. For the assay of Hydrastis, I prefer the periodide method of Prescott and Gordin. The method works nice and good results are obtained from it. Ipecac is a drug difficul to assay due to the ease with which the alkaloid decomposes and is lost. I pre- fer the Prollius method and precipitation with Mayers Reagent (367). I have found the result obtained by this method more trustworthy than those obtained by any other method. fhe assay of Nuxvomica is best worked by the Per- iodide method of Prescott and Gordén. Dragendorff's method (888) is efficient although is consumes a good deal of time. The short assay method of (71) also gives good results. Opium presents several forms of assay methods. I always use the method of J. Howard Wainwright of the U. S. Labratory of Custom House (417). It yields by far the-best results. Prescott's method also yields good results. Physostigma or Calabar Bean is best standardized by (440.) The alkaloids are here determined as tov alkaloids and not separately. For Pilocarpus I prefer the routine. of (71). The s of (62) et segs, gives practically identical he assay of Pulsatilla is new and very little is known about it. The assay of (450) is based upon the assumption that the active principle anemonin is 2 neR- tral substance. The exact estimation of strophanthin, the active principle of strophanthus, is no easy task. Elbornes method (458) gives the best results although duplicates never agree very closely. Veratrum is another drug added to the list of those as yet imperfectly know. The assay process (71) gives best results but very little choice. here is a large field open to the Pharmaceutical Chemist for work and research. Very few of our now largely used drugs have been accurately analyzed and their constitutents determined. The work must came from our Universities, as the Pharmaceutical Chemists employed in manufacturing have little or no time for this class of work. We trust that more of our Univer- sity students will publish their work alon this line, so that we who are engaged in manufacturing may learn more of the theoretical side of these now uncertain and unstudied drugs. The greater part gf the research and library work was performed through Be permission of Prof. J.W. Lloyd, as well as to Dr. Waldbott, the librarian, I am deeply indebted. The researches have covered all copies of the fol- lowing publications from first copy issued to Jan. Ist, 19013-- Conipt. Rends American Jour. Pharmacy; Pharm. Zeitung; Archives of Pharmacy; Haudbuch der Pharma- ceutischen Praxis; Pharm. Ceutralhs American Drup- gist; Jour. Pharm. Chim; Pharm. Rundschaws; Schweig Wochenschrift p. Chem. we Pharmacy; Bulletin of Pharn.; Jour. Anal. & Applied Chemistry; Jorn. Amer. Chem. 50- ciety; Chemical Zietungs; Chemist and Druggist; Pharm. Review; Pharm. Journal; Pharmaceutical Record; Pharm Journal and Trans of Englands Dingler's Polyteenic Jour nal3 Ztschr fur Anal. Chenils Apoth. Zietungs Proc. American Pharmaceutical Association; Merck's report; Pharmaceutical Post3 Zeitschr Obes; New Remedies; Year-Book of Pharmacy3 Squibb'’s Hphemeriss The Hague; The Analyst; Druggist’s Bulletin; Ibid; Pharmaceu- tical Erag Chemical News; British and Colonial Drug- gist and the National Druggist. References marked throughout Thesis. (1) Compt. Rend. 100% 750. (2) Drageudorff's Plant Analysis. (8) Pharm, Zeitung 1897, No. 89 Reprint Am. Jour. Pharmacy January, 1880. (4) Handbuch der Pharmaceut. Praxis p. 62. (5) Arch. Pharm. 1881 - 1885: Reprint Am. Jour. Pharmacy 18823 59. (6) Pharm. Ceutralh, 315 888, 771 Am. Druggist 1891; 351. (7) J. Pharm. Chim. 18933 p. 99, 162. (8) Schweig. Wochenschrift f. Chem. u. Pharm. 1892; 501, 509. (9) Pharm. Rundschau. 189383 282. Pharm. Rundsbhau. 13943 36. reprint --rnBulletin of Pharmacy 18983 535.37. reprint -- Bulletin of Pharmacy 1894; 95-95%. (10) American Druggist May 15th, 1892. Journ. of Ahal. and applied Chem. Vol. 6, Mar? 1892. (11) Am. Jour. Pharm. 18953 499, 509. (12) Jour. Am. Chem. Soc. 18993 281, 2385. (18) Chem. Ztg. Oct. 4th, 1890. Chem. and Druggist, 18903 602. Pharm. Review Nov. 1899. p. 495 ~ 496. Phar a 2: 318, Pharm. Jour. Sept. 28d, 1899. p. 295 Comp. Rend. L293. 110. fhe figures in the table, except those for gel-~ semine and cocaine, are from Doagendorff's Plant Analysis. Art. 173. Pharm Record. 18863 209, Jour. Am. Cheme Soce Sept. 1898. p. ? Gpmberg. Jour. Am. Chem. Soc. 183 339. Phar. Jour. Trans. 18803 p. 809. Dingler's Poly*t Jour. 1613; 140. Zeitschr. Anal. Chem. 13 102. Ztschr. Anal. Chem. 343 294, 407. Apath. Zeit. 123 459, 467. Pharm. Jour, Tran. (2nd series - Vol. 6, 275). Prescott's Preanic Analysis 18873 46, Zerich. Chemische Ermitt. won Giften 1876, 141. Amer. Jour, Pharm. Vol. 71, No. 11 pe 1, 1899. JeW. Loyd, Proc. Am Ph. Ass. 18913 128. Lyons preferred. J. Steiglitz, Pharm. Randschair, N. Ye, 18913287. FeAe Thompson. Proc. Am Pharm Assoc. 1892, 446. reprint from Proc. Miche Pharm Assoc. 1891. Je Katz - Arch. de Pharm 1898. Amer. Drug. 18983 231. Runds f. Pharm 21, 327, Pharm Post. 1895, 226. Pharm. Ceutralh 18393 117, Am. Jour. Pharm. 18873 179. reprint from Pharm Ceutralh 13873 602. Pharm. Ceutralh 18873 508. Pharm. Runde 18913 240, Apodth. ZeitR. 1891; 538. Pharm. Ceutralh 18903 588, 771. Pharm. Reviewv. 17, 495, ferck's Report 18993 467, Pharm. Rundschaw 18993 136, Merck's Report 19003; 417. By EH. Richards and Ashley Rogers in Chem. and Druggist. 1891; 208 -~ 2492, Pharm Jour, Trans. 18963 122, Transe Am Pharm. Assoc. 1385; 589-40. Pharm. Jour. Brans. 18913 280. Transe Ame Pharm. Assoc. 18953 54 Pharm Zeitschr f. Russl. 18973 65, Pharm. Ceutralh, No. 12, 1885. Proce Soce mp. de Med. Constantinople 1896. Zeit- schr Olst. Apoth. ver 18963; 766, (48) Brans. Am. Pharm. Assoc. 18943 588.40. (49) Pharm. Rundsch. 18933 282. (50) Pharm. Jour. and Trans. 1334; 9283, (51) Pharm Jour. and Trans. 18853 287. (92) Pharm. Jour. and Trans. 18393 298. (538) Pharm Jour. and Trans. 18393 295 Amer. Jour. Pharm. Vol. 71, No. 8. (54) Pharm Review 1898; 324, (55) Chem. and Drugg. 18903 154, Amer. Jour, Pharm 18913 12, Trans. Amer. Pharm. Assoc. 1891; 463. (56) Amer. Jour. Pharm. 1834; 570. (58) Prac. Amer. Pharm. Assoc. 18923 261. (98) Schwz. Wochen fu. Pharm. 18913 147, (99) Pharm. atg. 18923; 750 reprint from Schwig. Wochen- schr. 30; 473, — (60) Handbuch der Pharm. Praxis 1; 828. (61) Amer. Drugs Oct. 18893 196, Compt. Rend. 1083; 750. (62) Pharm. week blad. 1898. Amer. Drugg. and Bharm Review 1893; 372. Pharm Ceutralh 189383 289. Trans. Amer. Pharm Assoc. 189 83 404.5, (63) Amer. Jour. Pharm 1891; 347-8. Transe Amer. Pharm Assoc. 1892; 745. (64) Trans. Amer. Pharm. Assoc. 1894; 542 - 43, Pharm Rund. 18943 527. Bulletin Pharm. 18943 56, (SO) New Remedies 18823; 258. Amer. Jour. Pharm. 18823; 548-50. (66) Apoth. Ztg. Dec. 8, 18983 848, Arche de Pharm. 18983 No. 8. Trans. Amer. Pharm. Assoc. 18993 541, (67) Pharm. Ztg. Sept. 24, 1898; 683. Iranse Amer. Pharm. Assoc. 18993 787. (68) Hphemeris, July 18993; 2314-2320. (69) Pharm. Jour. and Trans. 1875; 461. The Hague July Sth, 1880, (70) Chemist ahd Druggist 18843 60. (71) Arche Pharm 283 81, 209. (72) The Analyst 1880 3 228. (73) Pharm. Round. 18943 57, Bulletin Pharmacy 18943 56, Trans. Am. Pherm. Assoc. 18943 542.438, (?4) Trans. Amer. Pharm. Assoc. 18943 544, Pharm Rund. 18983 283. Drugee Bulletin 18983 534. : . " . ” . : : (75) Jour. Pharm. Chem. 18983 99, 152, (?6) Hphemeris Jume 18883 116-106. (7?) Amer. Jour. Pharm. 18883; 2388, (78) Pharm, Ztst. furr Russ. 18893 349, Med. Tids. Pharm. 893 116, Pharm. Zteg. 893 282. (79) Trans. Am. Pharm. Assoc. 18973 538.39. harm. Jour. Apr. 19, 1896. (80) Trans. Amer. Pharm. Assoc. 1894; 544.45, Pharm. Rund. 18943; 282, Drugge Bulletin 189383; 534, ($1) Pharm. Record 18983 282, (82) by B. Leljenstrom, Pharm. Ztg. 18943; 57%. (88) Pharm, Jour. Trans. (3d series) 218, p. 1, 511, 820, 888. (84) Schevis Wochen, fu. Chem. et Phar. 1894. (85) Chemist and Druggist 18923 263, (86) Jour. Am. Chem. Soc. 18963 183 331-42, (87?) Amer. Drug. May 15th, 1892. Prof. Amer. Pharm. Assoc. 18923 483. (88) Jour. Pharm. Chem. v. 33 529. Chen. Ceutralh 1396, v. 2, 214. (89) Proc. Amer. Pharm. Assoc. 18963 559. (90) Proc. Amer. Pharm. Assoc. 18953 3385. (91) Proc. Amer. Pharm. Assic. 18973 53 (92) Mich. State Board Assoc 1893, Trans. Amer. Pharm. Assoc. 1893, (93) Transe Amer. Pharm Assoc. 18943; 546-48. Wochenschr f. Chem. et Pharm. 1894, Apath, Zeit. 1894; 52, 133, (94) Trans. Amer. Pharm. Assoc. 1894; 546.47, Amer. Journal Pharm. 18983 374. (95) Trans. Amer. Pharm. Assoc. 18953; 546-47, Amer. Drug. and Pharm. Rev. 18943 55, Schweitz Wochenschr. f. Chem. p. Ph. 1894. Apoth. Ztg. 18943 52, 133. (96) Pharm. Era Apr. 7th, 1898. ‘) Trans. Amer. Pharm. Assoc. 18983 688-89, (97) Pharm. Ceutralh, Nov. 8d, 18983 787, Transe Amer. Pharm. Assoc. 18993 429-30, (98) Amer. Jour. Pharm. June 18993 257.66, (99) Jour. Pharm. Trans. 18943; 396, Ibid. 1895 (1) 61, amd 1895, (2) 378, 641, 690. (100) Pharm. Jour. Trans. 18963; 321. (101) Pharm. Jour. Trans. 18893 721. (102) Pharm. Post. 1892; 913, 983. (103) Apoth. Ztg. 18903 781. (104) Amer. Jour. Pharm. 18883 531. (105) Amer, Jour. Pharm. 1892; 62. (106) Schweitz. Wochen fur Phar. 1893; 473. Trans Amer. Pharm. Jour. 18943 549-50. (107) Merck's Report Oct. 18993 469. (108) Pharm. Jour. Trans. Feb. 17th, 18883 665-66. Amer. Jour. Pharm. 553 263-69, (109) Trans. Amer. Pharm. Assoc. 18383 246. (110) Trans. Amer. Pharm. Assoc. 18913; 91-98. (111) Schweiz Wochensch 333; 452, Trans. Amer. Pharm. Assoc. 1894; 529-30. (112) Trans. Amer. Pharm. Assoc. 18943 550. Bull etin Phermacy 18943 57. Pharm. Rund. 1894; 59. (113) Amer. Jour. Pharm. 1896; 189. (114) Chemische Werthbestimuming 1896; 61. Trans. Amer. Pharm. Assoc. 1896, (115) Pharm. Jour, 1899 (4th series) De. 20. Amer. Journal Pharmacy 713 10. (116) Merkk's report 1899; 468569. (117) Proc. Amer. Pharm. Assoc. 18943 531. (118) Proc. Amer. Pharm. Assoe.1898; 165. (119) Arch. de. Pharm. 1889; 158. Amer. Jour. Pharm. 18893 180, (12) Pharm. Ceutralh 1887; 508. (121) Proc. Amer. Pharm. Assoc. 18983 10%. (122) By H. Ce. Plugge, Arch. de Pharm. 18873 340? Pharm. Zeitung No. 603 1882. Jour. de. Pharm. de Alsace, Lorraine, 1882. (124) Trans. Amer. Pharm. Assoce 18883 372. (125) Trans. Amer. Pharm. Assoc. 18883 374. Amer. Drug. 18873; 143.44, Pharm. Ceutralh, 1887 No. 21. (126) American Drug. 1838; 104. (127) Trans. Amet. Pharm. Assoce 1890- 667-638, Trans. Amer. Pharm. Assoc. 18903 473; 474. (128) Jour. Amer. Chem. Soc. 73 48. (129) Apoth. Zietg. 18913 026. (180 Pharm. Jour. 18973 202. (181) Brit. and Coll. Druggist 18943 372. Trans. Amer. Bharm. Assow. 1894; 552. (182) Jour. Chem. Soc. Nov. 1884; 1217. (133) Pharm. Ceutralh April 2nd, 1896; 209. Trans. Amer. Pyarm. Assoc. 18963 612- 13, . ° > : ~ ° : (184) Jour. Chem. 50c. 18983 ve 113 2¢l1. (185) Jour. Amer. Chem. Soc. 18983 720. (136) Amer. Jour. Pharm. 19003 36-39. (137)cAmer. Jour. Pharm. 18943 136. (1388) Yearbook gf Pharmacy 1881; 26, 141. (189) Yearbook of Pharmacy 1887; 423. (140) Pharm. Jour. Trans. Nov. Sth, 1896; 463. (141) Proc. Brit. Pharm. Ciufer? 13983; 358.59. (142) Pharm. Poste 18893 227. (143) BY Chas. Bullock Amer. Jour. Pharm. 1879; 333. (144) Proc. Mich. State Pharm. Assoc. 1886. narmaceutical Era 13873; 12. PNIVER SITY ©OF LEmUN Ors THIS IS TO CERTIFY THAT THE THESIS PREPARED UNDER MY SUPERVISION BY \ ) oes y : i ee ENTITLED K 7 : LV AN Va IS APPROVED BY ME AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE OF : , 4 MEAD OF DEPARTMENT OF V 2 a | UNIVERSITY OF ILLINOIS-URBANA INIA 3 0112 086855217 te ee ee