67d 



tHE TROPICAL AGRICULTURIST, [Ami t, 1887. 



improtant to ascertaia the presence and amoant of 

 tbit» imparity ia the qaiuiae salpbate of commerce. 



Wfleu we call to mial the fact that ciucbOQidiae 

 is almost always associttod with quiniae ia the 

 bark from which qaiuiae sulphate is miimfj,ctured, 

 and also the fact taat up tj trie yeir 13U ciuchon- 

 idiue WIS njt kaowu as an in iepeu leut subitvace 

 distinct from qiinine, it will be evident that there is, 

 on these grounds aloae, very g-)oJ reasjn for believing 

 that prior to tlie daoe meutioue 1 the article kuowa 

 as quiuiue suipbate was really a tnixtnre of the sul- 

 phates of qaiuiue and cinch )iii line. It would be 

 possitjle to mention in support of this view many 

 circumstaices recjrded oy trustworthy observers, 

 but I w 11 merrily rerer to the fact lately made known 

 by Dr. deVrij that the qiinine sulphate origiuady 

 manufictured oy Pelletier cuutaiuPi a cousideraOle 

 amjuat of cinch miline. 



Wiuckier's identifioition of cinchonidine, in 1844, 

 was c'ji icident with the introduction of bark from 

 New Grenada, to supply ttie pUce of the Bjiivian 

 bark tbat Dad been previously used for the manu- 

 facture of quinine, and the fact that this New 

 Grenada bark contai led a much larger amount of 

 cincho.iidiue than Bjliviau bark was, no doubt, the 

 circumstance which led to the identification of the 

 alkdluid. Unfortunately, Winckler gave it the name 

 of "quiuidine, " and very shortly afterwards the 

 sulphate of this a'kaloid was met with in commerce 

 under the name of "qainidine. " At the 1851 Ex- 

 hibition it was shown by Zimmer, of Frankfort, and 

 a prize was then awarded to his firm for its produc- 

 tion in a separate form. Probably it had been used 

 long before as an adulterant of quinine sulphate, 

 and as the methods of testing the purity of quinine 

 su'phate in use at that time were not calculated to 

 detect the presence of the cinchonidme salt, there is 

 also a probability that it was often present to a con- 

 siderable amount in commercial quinine sulphate 

 as an accidental and to a large extent quite unrecog- 

 nized impurity, originating from the mat-rial used. 

 The literature ot that period indeed furnishes abun- 

 dant evidence of this, and several new methods of 

 testing were then suggested for the detection of cin- 

 chonidine. None of them, however, were thoroughly 

 effectual, and the official tests given in the vaoous 

 pharamacopceias were all of such a nature that a 

 cousiderable amount of cinchonidine salt would pass 

 unrecognized. That has, indeed, been the case up 

 to tne present time. 



It is evident, therefore, that the presence of cin- 

 chonidine sulphate in commercial quinine sulphate 

 caunot be regarded as a matter of any novelty, either 

 as an unrecognized accident before 1814, or as a w<-ll 

 undei stood fact since that time; but that, on the 

 contrary, it was a natural consequence of the asso- 

 ciation . of cinchoniJine with quinine in all the 

 va ieties of material employed tor the manufacture 

 of quinine sulphate. The quesdou as to the purity 

 of tnis salt, apart from actual fahificatioo, has there- 

 fore alway.s been a question as to the actual amount 

 of cinchonidine it contained. It is mainly in regard 

 to this particular point that the value and efficiency 

 of the tests applied for ascertaining the purity 

 of qiinine sulphate require to be considere i. and 

 it is now just ten yeirs ago that I pointed out 

 the defective nature of the test prescribed in the 

 British pharmacopoeia of 1867. I tiien showed that 

 by the application of the Pnarmacopana test a sample 

 of quinine sulphate containing at least 10 or 15 per 

 cent of cinchonidine sulpate could not be dis- 

 tinguished from one of absolute purity, or contain- 

 ing no more than one per cent, and that while there 

 were somti manufacturers who suppue I the article 

 in a comparatively high state o'' purity, that obtained 

 from other sources often contained a large amount 

 of the cinchjnidine salt. The existence, even in 

 the past, of such diirerence.s in the qiality of a 

 medicinal agent so important as quinine sulphate, 

 and thrt potsibi'iiy of their recurrence, should cer- 

 tainly inluced phiramajists to give attention to this 

 matter, and to verify tne qadic/ of their supplies 

 by careful ex^ainiuatioa, not only lor the iiake of 



their own protection, but also for the parpose of 

 enabling them to furnish a personal guarantee an to 

 the purity of this article. 



The methods of testing quinine sulphate for as- 

 certaining its purity and detecting the presence of 

 salts of the other cinchona alkaloids are for the most 

 part based upon the relative solubility of those alka- 

 loid.- in ether or in ammonia, and partly, also, upon 

 the relative sdubility of the neut a) sulphates of 

 those a kaloids in water. As already mentioned, 

 the problem to be solved, under ordinary conditions, 

 is a simple one, and it may be stated in these terms: 

 What is the amount of cinchonidine sulphite present , 

 The ether test was first applied for this purpose ia 

 1852. It consisted in shaking a weighed quautitj of 

 the sulphate in question with ether and ammonia 

 in a teat lube, anl if the alkaloid set free by the am- 

 monia was completely dissolved by the ether, forming 

 a clear solutou, the sulphate was considered to be 

 free fro.n objectionable impurity. But the ether 

 test thus applied is not sufificiently delicate for the 

 purpose required. Freshly precipitated quinine dis- 

 solves readily in a very small proportion of ether, 

 and the solution remains quite clear if the evapor- 

 ation of the ether be prevented. Cinchonidine is 

 also soluble in ether, but to a very much smaller ex- 

 tent. Thus, for example, 10 grains of quinine sul- 

 phate treated in this way, with I drachm of ether and 

 some ammonia, will give a clear solution ; but 1 grain 

 of cinchoiii line sulpate gives a very different result 

 when so treated, a large portion of the aikaloid remain- 

 ing undissolved by the ether. The actual limit of 

 -olubility of cinchonidine in ethi^r is reached when the 

 sulphate is in the propotion. of about half a grain to 

 the fluid drachm of el her. Hence it might be expected, 

 that when this test is applied to a sample of quinine 

 su'phate containing 10 per cent of cinchonidine 

 sulphate, the presence of this impurity would be as- 

 certainable. Tnat is not the case however. When 

 such a sample is tested in this away, the whole of 

 the alkaloid is dissolved, forming a clear solution, 

 and there is no indicaton of the presence of cin- 

 chonidine. The fact is, that an ether solution of 

 quinine dissolves more cinchonidine than an equal 

 volume of ether does. The practical result is that 

 the ether test applied in the manner just described 

 will not in any case indicate the presence of cin- 

 chonidine unless its amount is upwards of 10 per cent 

 at least. 



It was partly in this respect that the ether test 

 as prescribed in the British Phaimaiopoeia, 1867, 

 the French Codex, 1866, and the United States 

 Pharmacopoeia, 1870, was defective. In each case 

 al-o there was the further mistake of directing too 

 large a proportion of ether to be used. Half an 

 ounce of et'ier, the quantity to be used, according 

 ta the B. P., with 10 grains of the quinine sulphate 

 to be tested, is capable of dissolving 2 grains of cin- 

 clionidine, and the 5 grams of ether to be used 

 with half a gram of the salt according to the 

 Codex, is sufficient to dissolve 00386 gram of cin- 

 chonidine, these quantities corresponding in one case 

 to about -0 per cent, and the other to 13 per cent 

 of cinchonidine sulphate that would escape recogni- 

 tion by the test. So far, therefore, as tnose official 

 standards were concerned, it is again evident that 

 the purity of qiuuine sulphate must be regarded as 

 having had up to within a very recent period only 

 a relative significance. 



[n the German Pharmacopoeia of 1872 Kerner's 

 test was adopted, and it h.is since been adopted in 

 the Uuite.l States Phirmacopojia of 1880. It is based 

 upon the fact that quinine is much more soluble in 

 ammonia solution than any oth-.c cinchona alkUoid. 

 When a cold siturated solution of n-ntral quinine 

 sulphate, containing' only from l-7U0th to l-800th of its 

 wei-ht of the salt, is mixed with ammonia solution, 

 the'alkaloi I precipitated in the first instance is 

 readilv dissolved again by adding more of the am- 

 m )nia' solution. If a volume equal to that of the 

 quinine s uphate solution bu adlel the mirtire be- 

 comes quite clear. When, however, a sa urated 

 solution of ciaehouidioe suipkAte ii> treated in tixn 



