The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan.

  • Buttle, G. A. H. (Gladwin Albert Hurst), 1899-1983.
Date:
[1934]
Catalogue details

Licence: Public Domain Mark

Credit: The action of the cinchona and certain other alkaloids in bird malaria. Pt. 2 / by G.A.H. Buttle, T.A. Henry and J.W. Trevan. Source: Wellcome Collection.

    7/22 (page 431)
    it to be a trihydrate. It is possible that in this case also Emde’s lower figures are in part due to incomplete drying. Assuming that Emde really used a monohydrate instead of the anhydrous salt for his determination, his figure would be raised to +217-9°, which on the basis of the present authors’ results would correspond to quinidine containing 6 % of dihydroquinidine. This calcu¬ lation assumes that the change in rotation due to dilution is the same and remains constant for quinidine and dihydroquinidine dihydrobromides. This is approximately true so far as the dilutions from 31/ 10 to 31/40 given in Table III are concerned, the two figures being 3-7 and 3-9°. The same assumption is made in the calculation for cinchonine given above and in this case the difference due to dilution of the dihydrobromides from 31/10 to 31/40 is 2-6° for both cinchonine and dihydro cinchonine. Two further comparisons are possible with the results recorded in Table III. The Dutch Pharmacopoeia permits a range of —17-7° to —18° for the observed rotation of 31/10 solutions of quinine and its salts taken under specified con¬ ditions as to solvent and temperature. Under these conditions 31/10 solutions of the quinine salts described in Table III gave the following results: mono¬ hydrochloride — 18-06°; neutral sulphate — 18-095° and acid sulphate —18-085°. Realising the lack of any method of eliminating the large quantity of di¬ hydroquinidine present in ordinary quinidine, a successful attempt was made recently [Butler and Cretcher, 1933] to prepare pure quinidine by re-arrangement of quinine [Rabe et al., 1932]. The yield was apparently small. The product had [a]x> + 323-8° (c = 2 in 1-8 % HC1). The pure quinidine used in the present investi¬ gation had [oc]p + 323T° observed under the same conditions. The specific rotations, calculated as base in Tables III and IV, bring out the interesting point that all eight alkaloids in the form of dihydrobromides show a lower specific rotation in 31/10 than in M/40 solution in water. It has not been possible to extend this comparison to other acid salts of all eight bases owing to the difficulty of getting satisfactory preparations of the complete series; the acid sulphates, for example, are too soluble to yield good preparations in some instances unless large quantities of the pure bases are available, and in other cases they cannot be dried completely without decomposition. It is however of interest to note that whilst quinine acid sulphate, like the dihydro¬ bromide, shows a higher rotation at 31/40 than at 31/10, cinchonidine acid suljffiate shows the same specific rotation at both concentrations. Determina¬ tions of pR of these solutions, for which the authors are indebted to Mr C. G. Pope, throw no light on these differences. Anomalies of this kind in connec¬ tion with the optical rotation of cinchona alkaloids have long been recorded [Oudemans, 1876] and have frequently been investigated, but so far no satisfac¬ tory and final explanation of their occurrence has been given. Preparation of the drugs. Separation of the primary alkaloids. It is easy to detect mere traces of quinine in cinchonidine, or of quinidine in cinchonine by the fluorescence of solutions in dilute sulphuric acid; and in purifying cinchonidine and cinchonine, each base was crystallised until a 1 % solution in Nj 10 sulphuric acid examined in bright, diffused daylight in a 2 dm. polarimeter-tube, showed no greater in¬ tensity of fluorescence than a 1 in 1,000,000 solution of quinine or quinidine re¬ spectively, examined in like manner. Under these conditions the fluorescence of quinine is just visible at 1 in 2,000,000. The inverse operation, viz. the detection of cinchonidine in quinine has been much investigated, and in practice there are two methods in use, viz. the 28—2