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LABORATORY 
 
 OF THK 
 
 INLAND REVENUE DEPARTMENT 
 
 OTTAWA. CANADA 
 
 BULLETIN No. 342 
 
 LIQUID EXTRACT OF NUX VOMICA. 
 
 7948-1 
 
■■ i 
 
 LABORATORY 
 
 OF THE 
 
 INLAND REVENUE DEPARTMENT 
 
 I ^ 
 
 BUI.T.KTIN No. 34:2. 
 
 LIQUID EXTRACT OF NUX VOMICA. 
 
 Ottawa, May 20. 1916. 
 
 J. U. Vincent. Esq., 
 
 Deputy Minister of in 
 
 lllli Kt'Vl'llUf, 
 
 SiH, — 1 beg to hand you herewith a report u|)Oii nineteen ( 19) samples of the Liquid 
 Extraet of Nux Vomica. This is not to be rotfarded a» a comprehensive inspection of 
 the important drug named, but as an attempt to ascertain what, if aiij-, ground exists 
 in fact for certain complaints made by physicians as to the varying and unsatisfactorj' 
 reeults ■ ' tained in practice with the Liquid Extract of Nux Vomica. The samples 
 now rei rted were purchased in Montreal and Toronto only. Their examination is 
 considered, as will be seen to justify a more extended inspection; and the present 
 report is to be regarded as preliminary. 
 
 It must be conceded that a certain dejfree of unsatisfactoriness exists regarding 
 the valuation of this drug. It is prepared from the seeds of Nux Vomica, in No. 20 
 powder, by repercolation with 70 per cent alcohol. The percolate from a given weight 
 of powder is equal, in units by measure, to the units of weight employed (grammes 
 and cubic centimetres) in the British Pharmacopoeia of 1898 ; in the revision of 1914, 
 the percolate is only half of this volume. In each case, the Btrychnine content of the 
 percolate is determined, and the Extract is finally adjusted by addition of 70 per cent 
 alcohol, to contain 1-5 percent of strychnine (weight in volume). 
 
 The seeds of Strychnos Nux Vomica contain two alkaloids, strychnine and brucinc. 
 whose physiological properties appear to be very similar, although the activity of bruciiie 
 is much less than that of strychnine. Thus, the dose of Str; chnine is fixed at %4 to Me 
 grain (B.P. 1914), while that of brucine is given as Vm to i grain. (Squires' Com- 
 panion to the Pharmacopoeia, Ed'n 1908.) Both of these alkaloids are naturally pre- 
 sent in the Liquid Extract ; and if they were present in the Seeds of Strychnos in a 
 co]\stant ratio, it would of course be possible to infer the amount of either by a deter- 
 mination of the other. Unfortunately this is not the case; and the ratio of strychnine 
 to brucine lias been found to vary between 3 to 1 and 1 to 2. (Squire, p. 810). 
 
 In the assay of the percolate from powdered Nux Vomica, the preliminary steps 
 are identical in both the 1898 and the 1914 editions of the British Pharmacopoeia. 
 The separation of the two alkaloids was effected, however, in the Edition of 1898, by 
 precipitation of the strychnine with potassium ferrocyanide, in sulphuric acid solu- 
 tion, and subsequent decomposing of the strychnine ferrocyanide. It has been found 
 by Schweissinger (Allen, Com. Org. Analysis, VI, 446) that under these conditions 
 brucine ferrocyanide is co-precipitated, to some extent, thus affecting the accuracy 
 of the method. 
 
 
Ill tlie Edition of 1914, the liruciuo i* Jentroyed by uxidation with nitric acid in 
 prewnce of tulphuric acid, and it it claimed that this method yields more acourata 
 i.sulU for sti7(4inine. In illustration of the reaultg of work done upon the Mm* 
 ';irnple by l«ith methods, I mii.v (juote the fo'lowinjj;— 
 
 """P'«- Method of 18»8. Method of 1»14. 
 
 •"" 1-46 ISJ 
 
 «««" 1-54 14B 
 
 «"2» lit 1-35 
 
 ""! 1'2« 1-24 
 
 «»»" 1-41» 1-J2 
 
 "•J? 0-8» 0-92 
 
 •<•*« 0*»6 0-»B 
 
 It will be seen that in most of these cases a somewhat higher apparent strychnina 
 I oiitent is obtained with the older (and now no longer official) method. 
 
 There can be no doubt that moat of the Liquid Extract of Nux Vomica now on 
 the mailet has been assayed by the method given in the pharmacopoeia of 1898; and, 
 indeed, in a strict sense this is the only method recognized by our Adulteration Act| 
 ill which Section 7 (a) specifically names the Edition of 1898. 
 
 Under these circomstances, and inasmuch as the collection of the samples now 
 Imported was restricted to two localities, I think it inadvisable that the names of 
 drillers or manufacturers (as stated by the vendors) should be given. 
 
 Quite apart, however from this consideration the results of analysis ore instruc- 
 tiv.s and serve to show that variations in the composition of the Liquid Extract of 
 Nux Vomica exist, apart from the strychnine content. 
 
 The analytical results given in the following table were obtained by Mr. A. J. 
 f.iindiy, of this staff, working by the official method of the British PhnrmacoDoeia! 
 Kdition of 1914. 
 
 UQUID EXTRACT OF M?X VOMICA. 
 
 Total Solid!. Alcohol. Strychnine. 
 
 Sample. arm. per 100 cc. Vol. p.c. Orm. per 100 cc. 
 
 64«2« 11-50 6»-72 0-78 
 
 64827 15'80 5»'72 l'J2 
 
 • 482$ 14-98 54-48 1-45 
 
 • 482* 17-07 50-98 l-JB 
 
 8481S 16-3S 86-82 1-44 
 
 •4«S1 11-00 38-18 0-91 
 
 •i4«'2 2-25 74-32 0-95 
 
 * - •• V 16-26 64-96 1-44 
 
 ' ' 11-78 88-32 1-57 
 
 15-92 58-96 0-78 
 
 ' -« 25-36 88-52 i'4« 
 
 -4#'. 15-42 56-92 i-3i 
 
 ■;2688 11-88 61-20 1-28 
 
 «28»7 13-50 67-56 1-82 
 
 «2«tl 18-06 50-32 1-59 
 
 62*»9 9-70 0.7. 
 
 62840 12-02 .... o-9« 
 
 «"«! »-44 48-44 l-ij 
 
 62*42 14-48 .... o-7« 
 
 Mr. Landry reports the usual difficulties attending the estimation of small quan- 
 tities of alkaloids in solution with fata, vegetable matters of varying kinds and mora 
 (.r less vegeUble tissue and colouring; and his duplicates indicate a variation of from 
 01 to 0- 15 in stiyshnine found. Accuracy is only possible where the mean of several 
 carefully conducted determinations is taken. 
 
 I know Mr. Landry to be a careful worker, and am convinced that the results 
 given indicate within very narrow limits, the actual strychnine present. The modvt 
 operandi for pr^Mration of the Liquid Extract is strictly defined by the pharma- 
 coiMjeia ; and, unlees the crude drug varies greatly in its quality, it is difficult to 
 account for the differences in total extractive matter, except on the assumption of 
 carelessness in manufacture. 
 
The British PhurmHoop.K'ia of 1SU8 di<l not staiidnrdiM' the powdi-ml ilniir. Th.- 
 edition of 1914 fixe^ thi« at IW per crnt of strychnine, and prefM-ribrs the addition 
 of milk sugar to adjint thi» value, within a limit of ac-uracjr of K> \h'T .-ent exerss 
 
 The total solidu are fm.,,.! to vary, in these samplea. from 2-25 per iwit to 25-2« 
 i)er eent. These extreme ditferences do ii..t .orresiiond to the variation in iitry<-hnnu> 
 conte.*- the sample jfivinn only 2 2-. per eent of total solid* contain* OW jR-r cent 
 of gtryei.nino; whilst that fciviug 2,". ;i« per .ent solids, yielda but 1-45 |K-r «-nt of thf 
 alkaloid. The phannaeoiKH-al staiulanl re<i»ire-i ir.O per cent strychnine. Most "f tl..- 
 samples which approximate to this perccntaKC show about 14 to 16 jK-r cent tot ,1 
 solids It aitpears reasonable to suppose that a normal Mmple of the crude dniK. 
 should on definite treatment as prescribed by the pliarmacoiMa-ia, yield an extract of 
 approximately constant character as n^ards dissolved soli<ls. This matter requin-s 
 investigation. . , , , . oi • . 
 
 Alcohol of 7(> Iter cent stn-ngth is iirescribe<l; and there" can U- no suWciciil 
 reason for a variation in strength of from Mfi-ie to 74-32 in the finished cxtra.-t. 
 
 I Ih>k to recommend that this subject be more fully inyestigaU-d iii the near 
 future; and that the present report be published as Bulletin No. 342. 
 
 1 have the honour to be. Sir, 
 
 Your obedient servant. 
 
 A. 
 
 M«<iILf.. 
 
 Chiff Aniil>i»t.