Estimation of the Alkaloids in Cinchona Bark—The microscope will enable us, as already shown, to ascertain whether a given bark is derived from Cinchona, but it can furnish no exact information as to the actual value of such bark as a drug.
Yet there is a very simple test by which the presence of a cinchona-alkaloid may be demonstrated. These alkaloids heated in a glass tube in the presence of a volatile acid or of substances capable of producing a volatile acid, evolve heavy vapours of a beautiful crimson colour, as mentioned [p. 363].
But to ascertain the real value of a cinchona bark, a quantitative estimation of the alkaloids is necessary. A good process for this operation has been given by De Vry.[1369] It is as follows:—Mix 20 grammes of powdered bark, dried at 100° C., with milk of lime (5 grm. slaked lime to 50 grm. water), dry the mixture slowly; by stirring it frequently, the cincho-tannic acid loses its solubility, being gradually transformed into cinchona-red. Then boil the dry powder with 200 cubic centimetres of alcohol 0·830 sp. gr. Pour the liquid on to a small filter, and afterwards the residual bark and lime mixed with 100 cub. cent. more alcohol. Wash the powder on the filter with 100 cub. cent. of spirit From the mixed liquids, about 370 cub. cent., separate the calcium by a few drops of weak sulphuric acid. Filter, distill off the spirit and pour into a capsule the residual liquid,—to which add a small quantity of spirit and water with which the distilling apparatus has been rinsed out. Let the capsule be now heated on a water-bath until all the spirit shall have been expelled; and let the remaining liquor which contains all the alkaloids in the form of acid sulphates be filtered. There will remain on the filter quinovic acid and fatty substances, which must be washed with slightly acidulated water. The filtrate and washings reduced to about 50 cub. cent., should be treated while still warm with caustic soda in excess. After cooling, this is decanted off from the precipitate, and then water added to it before throwing it on to a filter. It is then to be washed with the smallest quantity of water pressed between folds of blotting paper, removed therefrom and dried. The weight multiplied by 5 will indicate the percentage of mixed alkaloids in the bark.
To separate the alkaloids from each other, treat the powdered mass with ten times its weight of ether. This will resolve it into two portions—(a) insoluble in ether, (b) soluble in ether.
(a.) This should be converted into neutral acetates, and to the solution there should be added iodide of potassium, which will possibly separate a little quinidine. After removal of the latter (if present), add solution of tartrate of potassium and sodium, which will throw down in a crystalline form tartrate of cinchonidine; from the mother-liquor, cinchonine may be precipitated by caustic soda.
(b.) The ether having been evaporated, the residue is to be dried at 100° C. and weighed. It may in many cases practically be considered as consisting of quinine only. If however the estimation of quinidine (conquinine) and quinamine is required, the residue, or a determined portion of it, should be dissolved in acetic acid just as much as will be necessary for affording a neutral solution. From this the hydroiodate of quinidine is precipitated by means of an alcoholic solution of iodide of potassium. In the filtrate quinine may be precipitated by adding a few drops of dilute sulphuric acid and an alcoholic tincture of iodine. The herapathite thus formed ([see p. 360]) is collected after a day, dried at 100° and weighed; it then contains 55 per cent. of quinine.
After adding a few drops of sulphurous acid, the alcohol should now be evaporated from the fluid from which the crystals of herapathite have been removed, and caustic lye added, by which the amorphous alkaloids will be precipitated, including quinamine if present.
Uses—Cinchona bark enjoys the reputation of being a most valuable remedy in fevers. But the uncertainty of its composition and its inconvenient bulk render it a far less eligible form of medicine than the alkaloids themselves. It is nevertheless much used as a general tonic in various pharmaceutical preparations.
As to the alkaloids, the only one which is in general use is quinine. The neglect of the others is a regrettable waste, which the result of recent investigations ought to obviate. In the year 1866 the Madras Government appointed a Medical Commission to test the respective efficacy in the treatment of fever, of Quinine, Quinidine, Cinchonine and Cinchonidine. Of the sulphates of these alkaloids, a due supply, specially prepared under Mr. Howard’s superintendence, was placed at the disposal of the Commission. From the report[1370] it appears that the number of cases of paroxysmal malarious fevers treated was 2472,—namely 846 with Quinine, 664 with Quinidine, 569 with Cinchonine, and 403 with Cinchonidine. Of these 2472 cases, 2445 were cured, and 27 failed. The difference in remedial value of the four alkaloids, as deduced from these experiments, may be thus stated:—
| Quinidine— | ratio of failure per 1000 cases treated | 6 |
| Quinine | ”” | 7 |
| Cinchonidine | ”” | 10 |
| Cinchonine | ”” | 23 |