Amil i, mf.] ^m *fkOPitAt AGRietfttU^lSf. 



en 



same manner the result is very diflff^rent, because 

 oinchonidine is so very much less soluble iu ammonia 

 solution than quinine. Here then is a means of 

 distinguishing between these t^vo alkaloids, and the 

 further difference existing between the sulphates of 

 these alkaloids, in their solubiHty in water at the 

 normal temperature, admits of this means of dis- 

 tin tian b ing applied as a test for the presence of 

 cinchou di e sulphate in quinine sulphate. The way 

 IQ which this is done may be explained most readily 

 by taKing as an example the case of quiaine sul- 

 pha e c ncaining 10 per cent of the oinchonidine salt, 

 and api lying the test as directed in the German 

 Pbarmacopcoia. 



One grim of such a salt will contain 0'99 gram 

 quinine suiphate, and 001 gram of cinchonidine 

 ealc. 



The first step is to separate the two su'phates by 

 means of their very diffeieut solubility in water. 



For this purpose the sample to be tested is shasen 

 with ten times its weight of cold water, and if 

 the two sulphates were taken up in propoition to 

 tbsir lespective solubility in water, the cinchonidine sul- 

 phate dissolved would be sevon times as much as 

 the quinine sulphate, since cinchonidine sulphite is 

 Bolub e in about 100 parts of water ; while q nnine 

 sulph.te reqaires about 700 parts for solution. * That 

 is the assu option upon which Kerner's test was 

 founded, an 1 if it were correct, the solmion obtained 

 by shaking 1 gram of quiuine sulphate containing 

 10 per cent cmchouidint- sulphate with 10 c. c. of 

 Witer w uU con'ain 0'0143 gram quinine sulphate 

 and O'i gram of cinchonidine sulphate. If such a 

 80 a ion were really obtained under the conditions 

 men ioned, Kerner's test would be a very delicate 

 one. But that is not the case. The solution of the 

 •a phates is not determined altogether by their re- 

 •pectiye solubility, and for variouB, reasons it does 

 DOC take place at the normal temperature iu these 

 proportiojs so leadily as might be expected. The 

 coBsequeuce is that in applying this test to quinine 

 BU phate containing cinchonidine sulphate only a 

 portion of the latter salt is dissolved, and the portion 

 which i-i not dissolved escapes detection. This fact 

 was pci ited out by me ten years ago, in the paper 

 whicL I read at one of these evening meetings; but 

 as the test is described in the German and the 

 United Satea Pharmacopeias it has not received 

 Bufficient attention. Practically considered, the result 

 is that Kerner's test is not much better than the 

 ether tdst already described, although it would be a 

 very delicate one if rightly applied. 



16 is altogether useles* to apply so delicate a test 

 for cinchonidine, unless in making the solution to 

 which ammonia is applied that alkaloid is really 

 disso.ved out of the sample to be tested. This is not 

 done when cold water is used. Whether it be due 

 to the slow action of cold water upou cinchonidine 

 sulphate, or to the existence of a double salt, the 

 result is the same, pirt of the cinchonidine remain- 

 ing undi-solved and thus escaping notice. I may 

 here mention that I think there is some reason for 

 believing part of the cinchonidine may be present in 

 a free state, as it frequently happens that quinine 

 sulphate has a dtcidid alkaline reaction. If this be 

 the case the insufficiency of Kerner's test in such a 

 case would be quite intelligible. 



The same test is adopted in the French Oodex, 

 and the conditions I hare shown to be necessary are 

 to some extent provi led for by a slight modification 

 intended to meet t*ie d ifficulty that ha s ju^t been 

 * The solubility of neucral quimue sulphate is given 

 somewhat differently by authorities, and it is not always 

 quite the same for different samples. Taking the range 

 of variation above-mentioned the quantities contained 

 in 10 c. c. of the solution will be as follows— 



10 c. c. of the 

 For a solubility solution will 



of 1 part in con ain 



gram 

 70) parts of water at 60® F •0143 



7D5 „ „ .... 'om 



mentioned. That consists in warming the mixture of 

 quinine sulphate and water by immersing the tube 

 in warm water, and then cooling the solution to a 

 temperature of 15 ® 0, before adding ammonia to 

 the fliterwd liquid. It has been found, however, that 

 mere warming is insufficient to ensure the solution 

 of all the cinchonidine salt that may be present in 

 a sample of quinine sulphate, and that consequently 

 the application of the test in this way cannot be 

 relied upon to afford trustworthy indications of th« 

 purity of quinine sulphate. For that purpose it is 

 essential that the quinine sulphate tested bhould either 

 be dissolved in boiling water, or at least heated to 

 the boiling point with nearly enough water to 

 dissolve it at that temperature. It is only iu this 

 way that the whole of the cinchonidine sulphate can 

 he dissolved and brought into a condition to bo re- 

 cognizable on the subsequent addition of ammonia.* 

 Tne Commission apppointed by the Pharmaceutical 

 (Society of Paris to inquire into this subjrct has, 

 after some months of investigation, also arrived at 

 the same result, and therefore recommended that 

 the mixture of quinine sulphate and water should be 

 heated to the temperature of 60° 0. But that is 

 not sufficient to ensure the detection of all the 

 cinchoniiiine salt that may be present, nor do 1 

 think that it is in any case, from an analytical 

 point of view, a mode ot piocedure suffici* ntly precise 

 to furnish trustworthy results as to the actual amount 

 of cinchonidine sulphate, For various leasous, 

 economical or therspeuiical, it may be advisable or 

 expedient to recognize a ct-rtain limitation of the 

 purity 10 be demanded in quinine sulphate; but 

 that Would be most appropriately done by hpecityiiig 

 the amount of cincbo idiue salt thut is to be allow- 

 able. Such a practical regulation of the matter 

 does not, however, constitute any reason for making 

 analytical methods less precise and analytical results 

 less accurate than is consiscent witn the knowlelge 

 at our command. Any test that provides for over- 

 looking some portion of a substance to be detected 

 mu.-st be distrusted as unsafe. 



In the present Biitish Pharmacopoeia the facts 

 that I have previously pointed out have ' ow been 

 tak>Tn cognizance of and in accordance wiih them 

 an improved modification of the ether test is adopted 

 for the testing of quinine sulphate. Here the im- 

 possibility of obtaining correct results when operating 

 directly upon the sulphate to be tested is overcome 

 by having recourse in the first instance to a fractional 

 solution of the salt by heating it with water to 

 the boiling point, and then, after cooling and recrys- 

 tallizitiou of the quiuine sulphate, applying the 

 ether test to the cold mother liquor. By this meana 

 the greater part, if not all of the cinchonidine salt 

 will be dissolved, while the proportion of quinine 

 sulphate remaining associated with it in solution will 

 be so minimized as to admit of the presence of 

 cinchonidine being detected by the formation of a 

 crystalline deposit either immediately or after the 

 lapse of some hours. 



Taking a sample containing 10 per cent of cin= 

 chonidine, boiling 10 grains of it with 5 fluid drachms 

 of water, then coohug to 60® F, , and filtering, 

 such a solution is obtained. To get a good re- 

 sult the solution should be evaporated to about one= 

 fifth its volume before being shaken with ether and 

 ammonia, and then the presence of cinchonidine will 

 be distinctly indicated. Even 1 per cent of cin» 

 chonidine sulphate can be detected in this way with 

 certainty,t and it is very easy to tell whetbsr any 

 sample of quinine sulphate comes within the limit 

 of purity fixed by the Pharmacopceia of " not much 

 more than 5 per cent. " 



In regard to the testing of quinine sulphate the 

 British Pharmacopceia is now decidedly in advance 

 of other pharmacopoeias. The ether test as there 



*Even then more than one recrystallization will 

 generally be requisite. 



fWhen the amount of cinchonidine is small it is requi- 

 site to leave the closed tube for twelve hours or longer 



lov the lsxss»tioji, oi fht cr^stftl^ to taits pl^cfi. 



