The liber is traversed by medullary rays, which in cinchona are mostly very obvious, and project more or less distinctly into the middle cortical tissue. The liber is separated by the medullary rays into wedges,[1348] which are constituted of a parenchymatous part and of yellow or orange fibres. The number, colour, shape, and size, but chiefly the arrangement of these fibres, confer a certain character common to all the barks of the group under consideration.

The liber-fibres[1349] are elongated and bluntly pointed at their ends, but never branched, mostly spindle-shaped, straight or slightly curved, and not exceeding in length 3 millimetres. They are consequently of a simpler structure than the analogous cells of most other officinal barks. They are about ¼ to ⅓ mm. thick, their transverse section exhibiting a quadrangular rather than a circular outline. Their walls are strongly thickened by numerous secondary deposits, the cavity being reduced to a narrow cleft, a structure which explains the brittleness of the fibres. The liber-fibres are either irregularly scattered in the liber-rays, or they form radial lines transversely intersected by narrow strips of parenchyme, or they are densely packed in short bundles. It is a peculiarity of cinchona barks that these bundles consist always of a few fibres (3 to 5 or 7), whereas in many other barks (as cinnamon) analogous bundles are made up of a large number of fibres. Barks provided with long bundles of the latter kind acquire therefrom a very fibrous fracture, whilst cinchona barks from their short and simple fibres exhibit a short fracture. It is rather granular in Calisaya bark, in which the fibres are almost isolated by parenchymatous tissue. In the bark of C. scrobiculata, a somewhat short fibrous fracture[1350] is due to the arrangement of the fibres in radial rows. In C. pubescens, the fibres are in short bundles and produce a rather woody fracture.

Besides the liber-fibres, there are some other cells contributing to the peculiarity of individual cinchona barks. This applies chiefly to the laticiferous ducts or vessels[1351] which are found in many sorts; they are scattered through the tissue intervening between the middle cortical layer and the liber, and consist of soft, elongated, unbranched cells, mostly exceeding in diameter the neighbouring parenchymatous cells.

As to the contents of the tissue of cinchona barks, crystallized alkaloids are not visible. Howard has published figures representing minute rounded aggregations of crystalline matter in the cells, which he supposes to be kinovates of the alkaloids; and also distinct acicular crystals which he holds to be of the same nature. These remarkable appearances are easily observable, yet only after sections of the bark have been boiled for a minute in weak caustic alkali and then washed with water; it may well be doubted whether they are strictly natural. The liquids which are capable of dissolving the alkaloids in the free state do not afford any if they are applied to the barks. The alkaloids being contained in the bark in the form of salts, the latter are decomposed by caustic lye, and the alkaloids set at liberty assume the crystallized state. This is in our opinion the origin of the crystals under notice.

The greater number of the parenchymatous cells are loaded with small starch granules, or in young and fresh barks with chlorophyll. In several barks, as in that of C. lancifolia Mutis, numerous cells of the middle cortical layer and even of the medullary rays, are provided with somewhat thick walls, and contain either a soft brown mass or crystalline oxalate of calcium. These cells have therefore been called resin-cells and crystal-cells; they are mostly isolated, not forming extensive groups or zones, and their walls are not strongly thickened as in true sclerenchymatous tissue. If thin sections of the barks are moistened with dilute alcoholic perchloride of iron, the walls of the cells, except the fibres and the cork, assume a blackish-green due to cincho-tannic acid; this applies even to the starch granules.

Characters of particular sorts.—The modifications of general structure just described, are sufficient to impart a special character to the bark of many species of Cinchona, provided the bark is examined at its full development, the structural peculiarities being far from well-marked in young barks.

Thus it is not possible to point out any distinctive features for the Loxa Bark of commerce, because it is mostly taken from young wood. We may say of it, that neither resin-cells nor crystal-cells occur in its middle layer, that its laticiferous vessels become soon obliterated, and have indeed disappeared in the older quills; and that the liber-fibres form interrupted, not very regular, radial rows.

The quills of C. Calisaya display large laticiferous ducts, which are wanting in the flat bark. There is a peculiar sort of the latter called Bolivian Calisaya (already mentioned at p. 353), the flat pieces of which still possess very obvious laticiferous vessels. As to the liber-fibres of Calisaya bark, they are, as before stated (p. 356), scattered throughout the parenchymatous tissue or endophlœum. In the bark of C. scrobiculata, which might at first sight be confounded with Calisaya bark, the liber-fibres form radial, less interrupted rows. The microscope affords therefore the means of distinguishing these two barks.

The barks of C. succirubra are particularly rich in laticiferous ducts, mostly of considerable diameter, in which the formation of new parenchyme may not unfrequently be observed. The orange liber-fibres occurring in this bark are less numerous, more scattered, and of smaller size than in Calisaya. The fracture of Red Bark, especially the flat sort, is therefore more finely granular and not so coarse as that of Calisaya.

The structural characters of Cinchona barks may lastly be fully appreciated by examining barks of the allied genera Buena, Cascarilla and Ladenbergia, which were formerly known under the name of False Cinchona Barks. The microscope shows that the liber-fibres of the latter are soft, branched and long, densely packed into large bundles, imparting therefore a well-marked fibrous structure. The external appearance of these barks is widely different from that of true cinchona barks; none of them it would appear is now collected for the purpose of adulteration.

Chemical Composition—The most important and at the same time peculiar principles of Cinchona bark are the Alkaloids,—enumerated in the following table:—[1352]

B. A. Gomes[1353] of Lisbon (1810) first succeeded in obtaining active principles of cinchona, by treating an alcoholic extract of the bark with water, adding to the solution caustic potash, and crystallizing the precipitate from alcohol. The basic properties of the substance thus obtained, which Gomes called Cinchonino, were observed in the laboratory of Thénard by Houtou-Labillardière, and communicated to Pelletier and Caventou.[1354] Shortly before that time, Sertürner had asserted the existence of organic alkalis: and the French chemists, guided by that brilliant discovery, were enabled to show that the Cinchonino of Gomes belonged to the same class of substances. Pelletier and Caventou, however, speedily pointed out that it consisted of two distinct alkaloids, one of which they named Quinine, the other Cinchonine. In 1827 the Institut de France awarded to the two chemists for their discovery the Montyon prize of 10,000 francs (see page 57, note 4).

Cinchonidine (thus called by Pasteur in 1853) was first obtained and characterized under the name of Quinidine in 1847, by F. L. Winckler of Darmstadt, from Maracaibo Bark (C. tucujensis Karst.); and in 1852 it was more closely studied by Leers, still under the name of quinidine.

Cinchovatine, formerly stated to be a peculiar alkaloid, has been shown by Hesse in 1876 to agree with cinchonidine.

Quinidine is the name applied by Henry and Delondre to an alkaloid they obtained in 1833; its peculiar nature was not clearly proved until 1853, when Pasteur examined it, and 1857 when De Vry showed its identity with the Beta-quinine extracted in 1849 by Van Heijningnen from commercial quinoidin. The name quinidine having been since applied to different basic substances more or less pure, Hesse (1865) has proposed to replace it by that of Conquinine (Conchinin in German). The alkaloid is especially characteristic of the Pitayo barks, and also occurs in the Calisaya barks from Java.

Quinamine was discovered in 1872 by Hesse, in bark of C. succirubra cultivated at Darjiling in British Sikkim; it is also of common occurrence in the barks collected in Java. Conquinamine was extracted in 1873 by Hesse from old barks from British India.

Paricine is another basic substance discovered in 1845 by Winckler, in the bark of Buena hexandra Pohl. Hesse detected it along with quinamine in the bark of C. succirubra; its composition is not yet known.

Aricine, C₂₃H₂₆N₂O₄, and Cusconine, C₂₃H₂₆N₂O₄ + 2 OH₂, occur in the so-called false Cinchona barks of not ascertained botanic origin. These alkaloids differ in many respects from those of true Cinchona barks.[1355]

Pitoyine was pointed out by Peretti (1837), but Hesse has shown (1873) that the bark called China bicolorata Tecamez[1356] or Pitoya Bark from which it was obtained, is altogether destitute of alkaloid.

Lastly may be mentioned Paytine, C₂₁H₂₄N₂O + OH₂, a crystallizable alkaloid discovered in 1870 by Hesse in a white bark of uncertain origin.[1357] It is allied to quinamine and quinidine, but has not been met with in any known cinchona bark.

By heating for a length of time solutions of the cinchona alkaloids with an excess of some mineral acid, Pasteur (1753) obtained amorphous modifications of the natural bases. Quinine thus afforded Quinicine, having the same composition; cinchonine and cinchonidine furnished Cinchonicine, likewise agreeing in composition with the alkaloids from which it originates. These amorphous products may also be obtained by heating the natural bases in glycerin at 200° C., when a red substance is also formed. In quinine manufactories, amorphous alkaloids are constantly met with, being partly produced in the course of the manipulations to which the materials are subjected. Yet cinchona barks also afford amorphous alkaloids at the very outset of analysis, whence we must infer their existence in the living plant.

The name Quinoidine (or rather “Chinioïdin”) was applied by Sertürner (1829) to an uncrystallizable basic substance, which he prepared from cinchona barks, and found to be a peculiar alkaloid. The term has subsequently been bestowed upon a preparation which has found its way into commerce and medical practice, in the form of a dark brown brittle extractiform mass, softening below 100° C., and having usually a slight alkaline reaction. It is obtained in quinine factories by precipitating the brown mother-liquors with ammonia, and contains the amorphous alkaloids naturally occurring in the barks. Quinoidin should not be used unless, when previously dried at 100°, it proves to afford at least 70 per cent. of alkaloids soluble in ether.

Quinine and the allied alkaloids have not been met with in any appreciable amount in other parts of the cinchonas than the bark, nor has their presence been ascertained in other plants than those of the tribe Cinchoneæ.

Characters of the Cinchona Alkaloids.

1. Quinine.—It is obtained from alcoholic solutions, in prisms of the composition C₂₀H₂₄N₂O₂ + 3 OH₂, fusing at 57° C. The crystals may be deprived of water by warming or exposure over oil of vitriol, and they fuse at 177° C. The anhydrous alkaloid is likewise crystallizable; it requires about 21 parts of ether for solution, but dissolves more readily in chloroform or absolute alcohol. These solutions deviate the ray of polarized light to the left, and so do likewise solutions of the salts of quinine. Yet one and the same quantity of alkaloid exhibits a very different rotatory power according to the solvent used, though the volume of the solution remain the same. Even the common sulphate differs in this respect from the two other sulphates of quinine. The same remark applies to the optical power of the other alkaloids.

If ten volumes of a solution of quinine, or of one of its salts, are mixed in a test tube with one volume of chlorine water, and a drop of ammonia is added, a brilliant green colour makes its appearance. In solutions rich in quinine, a green precipitate, Thalleioquin or Dalleiochine is produced; in solutions containing less than ¹/₁₀₀₀ of quinine, no precipitate is formed, but the fluid assumes a green even more beautiful than in a stronger solution. The test succeeds with a solution containing only one part of quinine in 5,000, and in a solution containing not more than ¹/₂₀₀₀ of quinine, if bromine is used instead of chlorine.[1358]

The bitter taste of quinine is not appreciable in solutions containing less than one part in 100,000. The blue fluorescence displayed by a solution of quinine in dilute sulphuric acid is observable in solutions containing much less than one part in 200,000 of water; yet it is not apparent in very strong solutions.

Besides the common medicinal sulphate, 2 C₂₀H₂₄N₂O₂ + SO₄H₂ + 8 OH₂, quinine forms two other crystallizable sulphates, namely the sulphate, C₂₀H₂₄N₂O₂ + SO₄H₂ + 7 OH₂, and a third having the composition C₂₀H₂₄N₂O₂ + 2 SO₄H₂ + 7 OH₂.

Herapath, at Bristol, showed in 1852 that quinine forms with sulphuric acid and iodine a peculiar compound, Iodo-sulphate of Quinine, having the composition (C₂₀H₂₄N₂O₂)₄ + 3 (SO₄H₂) + 2 HI + 4 I + 3 OH₂. As this substance possesses optical properties analogous to those of tourmaline, it was called by Haidinger, Herapathite. It may be easily obtained by dissolving sulphate of quinine in 10 parts of weak spirit of wine containing 5 per cent. of sulphuric acid, and adding an alcoholic solution of iodine until a black precipitate is no longer formed. This precipitate is collected on a filter and washed with alcohol; then dissolved in boiling spirit of wine and allowed to crystallize. The tabular crystals thus obtained are extremely remarkable on account of their dichroism and polarizing power, as well as for the sparing solubility, since they require 1000 parts of boiling water for solution; their sparing solubility in cold alcohol may be utilized for separating quinine from the other cinchona alkaloids and estimating its quantity.

2. Quinidine or Conquinine—forms crystals having the composition, C₂₀H₂₄N₂O₂ + 2 OH₂; the anhydrous alkaloid melts at 168° C., and requires about 30 parts of ether for solution. Its solutions are strongly dextrogyre; it agrees with quinine as regards bitterness, fluorescence and the thalleioquin test, and forms a neutral and an acid sulphate. The most striking character of quinidine is afforded by its hydriodate, the crystals of which require for solution at 15° C., 1250 parts of water or 110 parts of alcohol sp. gr. ·834. Quinidine may therefore be separated from the other alkaloids of bark by a solution of iodide of potassium which will precipitate the hydriodate. According to Hesse (1873), quinidine is further characterized by the fact that its sulphate is soluble in 20 parts of chloroform at 15° C., the sulphates of the other cinchona alkaloids being far less soluble in that liquid. The common medicinal sulphate of quinine, e.g., requires for solution 1000 parts of chloroform.

3. Cinchonine.—This alkaloid forms crystals which are always anhydrous; they fuse at 257° C., and require about 400 parts of ether and 120 of spirit of wine for solution. Cinchonine further differs from quinine by its dextrogyre power, its want of fluorescence, and its non-susceptibility to the thalleioquin test. Its hydriodate is readily soluble in water, and still more so in alcohol whether dilute or strong.

4. Cinchonidine.—forms anhydrous crystals melting at 206° C., soluble in 76 parts of ether, or 20 of spirit of wine, then affording levogyre liquids, devoid of fluorescence, and not acquiring a green colour (thalleioquin) by means of chlorine water and ammonia. Hydrochlorate of cinchonidine forms pyramidal crystals of the monoclinic system, very different from the hydrochlorates of the allied alkaloids.

5. Quinamine.—The crystals are anhydrous, fuse at 172° C., and form at a temp. of 20°, with 32 parts of ether or 100 parts of spirit of wine, a dextrogyre solution. Quinamine is even to some extent soluble in boiling water, and abundantly in boiling ether, benzol, or petroleum ether. The solutions of quinamine do not stand the thalleioquin test, nor do they display fluorescence; in acid solution, the alkaloid is liable to be transformed into an amorphous state. Quinamine moistened with concentrated nitric acid, assumes like paytine a yellow coloration. Its hydriodate is readily soluble in boiling water, but very sparingly in cold water, especially in presence of iodide of potassium, in which respect it is allied to quinidine as well as to paytine.

The more important properties of the Cinchona alkaloids may be summarized as follows:—

Proportion of Alkaloids in Cinchona Barks—This is liable to very great variation. We know from the experiments of Hesse (1871), that the bark of C. pubescens Vahl is sometimes devoid of alkaloid.[1359] Similar observations made near Bogota upon C. pitayensis Wedd., C. corymbosa Karst., and C. lancifolia Mutis, are due to Karsten. He ascertained[1360] that barks of one district were sometimes devoid of quinine, while those of the same species from a neighbouring locality yielded 3½ to 4½ per cent. of sulphate of quinine.

Another striking example is furnished by De Vry[1361] in his examination of quills of C. officinalis grown at Ootacamund, which he found to vary in percentage of alkaloids, from 11·96 (of which 9·1 per cent. was quinine) down to less than 1 per cent. An extremely remarkable variation has also been displayed, as already alluded to at p. 351, by Ledger’s Calisaya.

Among the innumerable published analyses of cinchona bark, there are a great number showing but a very small percentage of the useful principles, of which quinine, the most valuable of all, is not seldom altogether wanting. The highest yield on the other hand hitherto observed, was obtained by Broughton[1362] from a bark grown at Ootacamund. This bark afforded not less than 13½ per cent. of alkaloids, among which quinine was predominant. In Java too, Cinchona Ledgeriana (see pp. 341, 351) has proved since to afford much more alkaloid than any American barks; as much as 13·25 per cent. of quinine have been observed in its bark.

The few facts just mentioned show that it is impossible to state even approximately any constant percentage of alkaloids in any given bark. We may however say that good Flat Calisaya Bark, as offered in the drug trade for pharmaceutical preparations, contains at least 5 to 6 per cent. of quinine.

As to Crown or Loxa Bark, the Cortex Cinchonæ pallidæ of pharmacy, its merits are, to say the least, very uncertain. On its first introduction in the 17th century, when it was taken from the trunks and large branches of full-grown trees, it was doubtless an excellent medicinal bark; but the same cannot be said of much of that now found in commerce, which is to a large extent collected from very young wood.[1363] Some of the Crown Bark produced in India is however of extraordinary excellence, as shown by the recent experiments of De Vry.[1364]

As to Red Bark, the thick flat sort contains only 3 to 4 per cent. of alkaloids, but a large amount of coloring matter. The quill Red Bark of the Indian plantations is a much better drug, some of it yielding 5 to 10 per cent. of alkaloids, less than a third of which is quinine and a fourth cinchonidine, the remainder being cinchonine and sometimes also traces of quinidine (conquinine).

The variations in the amount of alkaloids relates not merely to their total percentage, but also to the proportion which one bears to another. Quinine and cinchonine are of the most frequent occurrence; cinchonidine is less usual, while quinidine is still less frequently met with and never in large amount. The experiments performed in India[1365] have already shown that external influences contribute in an important manner to the formation of this or that alkaloid; and it may even be hoped that the cultivators of cinchona will discover methods of promoting the formation of quinine and of reducing, if not of excluding, that of the less valuable alkaloids.

Most salts of the alkaloids of cinchona afford a beautiful purple tar when they are heated in a test tube, and the same is also produced with the powdered bark, provided alkaloids be present. No other bark, as far as we know, yields a similar product of the dry distillation. It is not observed even in using true Cinchona barks, which are devoid of alkaloids. This method for ascertaining the presence of alkaloids in Cinchona barks has been proposed in 1858 by Grahe of Kasan. Hesse has improved Grahe’s test in the following way: he extracts the powdered bark with slightly acidulated water and dries up the liquid with a little of the powder. Grahe’s test at once shows whether a given bark contains Cinchona alkaloids or not.

Acid principles of Cinchona Barks—Count Claude de la Garaye[1366] observed (1746) a crystalline salt deposited in extract of cinchona bark, which salt was known for some time in France as Sel essential de la Garaye. Hermbstädt at Berlin (1785) showed it to be a salt of calcium, the peculiarity of whose acid was pointed out in 1790 by C. A. Hoffmann,[1367] an apothecary of Leer in Hanover, who termed it Chinasäure. The composition of this substance, which is the Kinic Acid of English chemists, was ascertained by Liebig in 1830 to be C₇H₁₂O₆, or now C₆H₇(OH)₄COOH. The acid forms large monoclinic prisms, fusible at 162° C., of a strong and pure acid taste, soluble in two parts of water, also in spirit of wine, but hardly in ether. The solutions are levogyre. Kinic acid appears to be present in every species, and also to occur in barks of allied genera; and in fact to be of somewhat wide distribution in the vegetable kingdom. By heating it or a kinate, interesting derivatives are obtained; thus, by means of peroxide of manganese and sulphuric acid, we get yellow crystals of Kinone or Quinone, C₆H₄O₂,—a reaction which may be used for ascertaining the presence of kinic acid. Kinic acid is devoid of any noteworthy physiological action.

Cincho-tannic Acid—is precipitated from a decoction of bark by acetate of lead, after the decoction has been freed from cinchona-red by means of magnesia. Dr. de Vry informed us that the Indian barks are usually richer in cincho-tannic acid; their cold infusion becomes turbid on addition of hydrochloric acid, which forms an insoluble compound with the former.

The cincho-tannate of lead decomposed by sulphuretted hydrogen, and the solution cautiously evaporated in vacuo, yields the acid as an amorphous, hygroscopic substance, readily soluble in water, alcohol, or ether. The solutions, especially in presence of an alkali, are quickly decomposed, a red flocculent matter, Cinchona-red, being produced. Solutions of cincho-tannic acid assume a greenish colour on addition of a ferric salt. By destructive distillation, cincho-tannic acid affords pyrocatechin.

Quinovic (or Chinovic) Acid, C₂₄H₃₈O₄, crystallizes in hexagonal scales which are sparingly soluble in cold alcohol, more readily in boiling alcohol, but not dissolved by water, ether, or chloroform. It occurs in cinchona barks, and has been met with by Rembold (1868) in the rhizome of Potentilla Tormentilla Sibth.

Other Constituents of Cinchona Barks—Quinovic acid is accompanied by Quinovin (or Chinovin), C₃₀H₄₈O₈, an amorphous bitter substance, first obtained (1821) by Pelletier and Caventou under the name of Kinovic Acid, from China nova,[1368] in which it occurs combined with lime. Quinovin in alcoholic solution was shown in 1859 by Hlasiwetz to be resolved by means of hydrochloric gas into quinovic acid, C₂₄H₃₈O₄, and an uncrystallizable sugar, Mannitan, C₆H₁₂O₅, with subtraction of H₂O. The formation of quinovic acid takes place more easily, if quinovin is placed in contact with sodium amalgam and spirit of wine, when, after 12 hours, mannitan and quinovate of sodium are formed (Rochleder, 1867).

Quinovin, although an indifferent substance, may be removed from cinchona barks by weak caustic soda, from which it is precipitable by hydrochloric acid, together with quinovic acid and cinchona-red. Milk of lime then dissolves quinovin and quinovic acid, but not the red substance. Quinovic acid and quinovin again precipitated by an acid, may be separated by chloroform in which the latter only is soluble, or also by cold dilute alcohol sp. gr. about 0·926, quinovin being readily removed by this liquid.

Quinovin dissolves in boiling water; its solutions, as well as those of quinovic acid, are dextrogyre. Quinovin seems to be a constituent of almost every part of the cinchonas and the allied Cinchoneæ, although the amount of it in barks does not apparently exceed 2 per cent. It is accompanied by quinovic acid: both substances are stated to have tonic properties.

Cinchona-red, an amorphous substance to which the red hue of cinchona barks is due, is produced as shown by Rembold (1867), when cincho-tannic acid is boiled with dilute sulphuric acid, sugar being formed at the same time. By fusing cinchona-red with potash, protocatechuic acid, C₇H₆O₄, is produced. Cinchona-red is sparingly soluble in alcohol, abundantly in alkaline solutions, but neither in water nor in ether. Thick Red Bark in which it is abundant, affords it to the extent of over 10 per cent.

The Cinchona barks yield but a scanty percentage of ash, not exceeding 3 per cent., a fact well according with the small amount they contain of oxalate and kinate of calcium.

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:—

The Indian Government, acting on the recommendation of Mr. Howard, has officially advised (Dec. 16, 1873) the more free use India of cinchona alkaloids other than quinine, and especially of sulphate of cinchonidine, which is procurable in abundance from Red Bark.[1371] Quinidine on the other hand, which has proved the most valuable of all, is only obtainable from a few barks and in very limited amount.

Dr. de Vry since 1876 advocates the use of what he calls Quinetum. This preparation is obtained by exhausting the barks with slightly acidulated water, and precipitating the whole amount of alkaloids by caustic soda. In India the remedy is known as “the Febrifuge.”[1372]

Adulteration—There is not now any frequent importation of spurious cinchona barks, but the substitution of bad varieties for good is sufficiently common. To discriminate these in a positive manner by ascertaining the percentage of quinine, which is the chief criterion of value, recourse must be had to chemical analysis, a method of performing which has been described. Entirely worthless barks may be easily recognized by means of Grahe’s test (p. 363). Modern Works relating to Cinchona.

The following enumeration has been drawn up for the sake of those desiring more ample information than is contained in the foregoing pages, but it has no pretension to be a complete list of all publications that have lately appeared on the subject.