Chapter LIV: Part 2 (15)

“Hydrated quercitrin forms microscopic, rectangular, partly rhombic tablets, having their obtuse lateral edges truncated; pale yellow when pulverised. It is neutral, inodorous, tasteless in the solid state, bitter in solution, permanent in the air.”[125]

[Footnote 125: Watts.]

=QUER′CITRON.= The bark of _Quercus nigra_ or _tinctoria_, a species of oak indigenous in North America. With alum mordants it yields a very permanent yellow dye.

=QUER′CITRON.= A yellow dye stuff, composed of the shavings and powder of the bark of _Quercus tinctoria_, or _Q. nigra_, or _Q. citrina_, a kind of oak, a native of North America. It abounds more particularly in Pennsylvania, Carolina, and Georgia.

In America quercitron is used for tanning, and in Europe for dyeing only. When employed for the latter purpose it is used in the form of an aqueous decoction, mordanted with alum or chloride of tin. Leesching states that a dye possessing greater colorific powder may be procured by boiling the bark with dilute sulphuric or hydrochloric acid.

=QUICK′SILVER.= See MERCURY.

=QUILLAI BARK.= _Syn._ QUILLAY BARK, SOAP BARK. The _Quillaya saponaria_, from which yields this bark, is an evergreen tree, growing in the mountainous parts of Chili, in South America.

It is believed to take its name from the native word _quillay_, which signifies to wash. The inner bark only is employed. When bruised and agitated in water it imparts a lather to the water, in the same way that soap does. This quality has been found to be due to the existence in the bark of _saponin_——the same principle which confers a similar property on _Saponaria officinalis_. The bark is free from any bitter principle, as well as from tannic acid. It is very generally used amongst the inhabitants residing on the western side of South America, where it is employed for removing grease from silk, and also in the form of a wash for cleansing and preserving the hair.

When had recourse to for cleansing silks, quillai bark is said not to change the colour of the fabric. It is sometimes given as a febrifuge, and as a remedy for cold in the head. For this latter purpose the powder is snuffed up the nostrils, when it occasions sneezing and profuse discharge from the nose.

=QUILLS.= _Prep._ 1. The quills or wing-feathers of the goose (goose quills) are separately plunged, for a few seconds, into hot ashes, cinders, or sand, of a temperature about equal to that of boiling water, after which they are scraped with a blunt knife, strongly rubbed with a piece of flannel or woollen cloth, and gently ‘stoved,’ they are, lastly, tied up in bundles by women or children. A yellow tinge is often given to them by dipping them for a short time into dilute hydrochloric or nitric acid, or into an infusion of turmeric.

2. Suspend the quills in a copper over water sufficiently high to nearly touch the nibs; then close it steam tight, and apply three or four hours’ hard boiling; next, withdraw the quills, and dry them, and in 24 hours cut the nibs and draw out the pith; lastly, rub them with a piece of cloth, and expose them to a moderate heat in an oven or stove. Quills prepared in this way are as hard as bone, without being brittle, and nearly as transparent as glass. Crow quills and swan quills may be cured in the same manner.

=QUI′NA.= See QUININE.

=QUINAMINE.= _Syn._ QUINAMINA. C_{20}H_{26}N_{2}O_{2}. This alkaloid was discovered by Hesse, in 1872, in the bark of _Cinchona succirubra_, cultivated at Darjeeling, in British Sikhim.

Dr de Vrij gives the following process for the preparation of quinamine:——The mixed alkaloids obtained from the red bark are converted into neutral sulphates, and the solution treated with Rochelle salt, whereby the tartrates of quinine and of cinchonidine are separated. After collecting these upon a filter the filtered liquid is shaken with caustic soda and ether. By this process the amorphous alkaloid and the quinamine are dissolved by the ether, with slight traces of cinchonine, whilst the bulk of this last alkaloid remains undissolved. After distilling the ethereal solution the residue is transformed into neutral acetate, and the solution of this mixed with a solution of sulphocyanate of potassium.

By this reaction the sulphocyanate of the amorphous alkaloid is precipitated in the shape of a yellow, soft, resinous substance, whilst the sulphocyanate of quinamine remains dissolved. After subsiding and filtering, the solution is clear and quite colourless, and by addition of caustic soda the quinamine is precipitated. It is then collected upon a filter, washed, and dried. It can now easily be obtained crystallised by dissolving it in boiling spirit, from which it crystallises in cooling. By this process the author obtained 0·38 per cent. of pure quinamine from samples of red cinchona quill bark, which he had received, through the Secretary of State for India, from the plantations in British Sikhim.

=QUINCE.= _Syn._ CYDONIA, L. The fruit of _Cydonia vulgaris_, or common quince tree. Its flavour in the raw state is austere, but it forms an excellent marmalade (quince marmalade), and its juice yields an agreeable and wholesome wine. The seed or pips (cydoniæ seminæ; cydonium——Ph. L.) abound in gummy matter, which forms a mucilage with water, and possesses the advantage of not being affected by the salts of iron or alcohol. See DECOCTION, FIXATURE, and JELLY.

=QUINETUM.= The alkaloids contained in the East Indian red bark (_Cinchona succirubra_) consist of a large percentage of cinchonidine, cinchonine, quinine, and amorphous alkaloid, besides a trace of quinidine, the preponderating alkaloid being cinchonidine.

Dr de Vrij, of the Hague, has devised a process by which these can be extracted in their entirety, and to the mixed alkaloids so obtained the name ‘quinetum’ has been given.

It is affirmed of quinetum that it possesses a remedial value as a tonic and antiperiodic that renders it, in many cases, superior to quinine, ague being one of these; also that it may be advantageously employed in affections in which quinine would be inadmissible. A medical correspondent informs us that he has used it with signal success in hay asthma. Another advantage it has over quinine is, it is much lower in price. Quinetum, according to Dr de Vrij’s process, as well as a sulphate and hydrochlorate, are prepared by Mr Whiffen, of Battersea.

=QUINICINE.= An alkaloid obtained in 1853 by Pasteur, by exposing quinine or quinidine, under favorable circumstances, to a temperature varying from 248° to 266° Fahr., for several hours. It is very probable that this alkaloid is either identical, or in very close connection, with the amorphous alkaloid soluble in ether which occurs in all barks, and particularly in the young barks of the plantations in India.

=QUINIDINE.= C_{20}H_{24}O_{2}N_{2}.2Aq. _Syn._ QUINIDIA, CONCHININE, &c. An alkaloid contained in many species of cinchona, together with quinine and cinchonine, and therefore often found in the mother liquors of quinine manufactures. It is identical with the β quinine of Van Heyningen, and was discovered, in 1833, by Henry and Delondre. As the cinchonidine discovered by Winckler, in 1848, has been unhappily denominated quinidine by this chemist, there is still a confusion about these alkaloids, and, therefore, the quinidine of commerce was very often a mixture of both, till Pasteur made, in 1853, a classical investigation of this matter. He maintained the name of quinidine for the alkaloid discovered by Henry and Delondre, because it is isomeric with quinine, and gives the same green colour when treated with chlorine followed by ammonia, and gave the name of cinchonidine to the alkaloid discovered by Winckler, because it is isomeric with cinchonine. He determined also the action of the solutions of these alkaloids on the plane of polarisation, and found that the quinidine turned this plane to the right, its molecular rotation in alcoholic solution being [_a_] = 250·75° →, whilst he found that the cinchonidine turned this plane to the left, its molecular rotation in alcoholic solution being [_a_] = 144·61° ←.

_Prop. &c._ Many of the salts of quinidine are very similar to those of quinine, but the normal salt with hydriodic acid is not only very different from that of quinine, but also from those of all the other cinchona-alkaloids. The normal hydriodate of quinidine is so very sparingly soluble in water that 1 part requires, at 60° Fahr., not less than 1200 parts of water to be dissolved. Therefore the presence of sulphate of quinidine in the sulphate of quinine, which often occurs, either from that article being carelessly made or from wilful adulteration, can be easily detected by adding a few minims of solution of iodide of potassium to the saturated solution of sulphate of quinine in water of 60° Fahr., whereby, if quinidine is present, its hydriodate will be separated either in the shape of a sandy precipitate or, if only traces are present, in the shape of striæ on the sides of the glass where this has been rubbed by a glass rod.

For an account of its medicinal properties, the reader should consult the recent report from India upon the experiments made there by order of Government with all the four cinchona-alkaloids, which experiments are very favorable to the therapeutical action of quinidine compared with that of quinine.

=QUININE.= C_{10}H_{12}ON. _Syn._ QUINA, QUINIA. Till recently it was found in the greatest quantity in good Calisaya bark, particularly in that from Bolivia, but since it has been found in great quantity in some other barks, especially in the bark of _Cinchona officinalis_, for instance, in the bark of that species grown in Ceylon. Red bark contains not only quinine and cinchonine, but also cinchonidine.

_Prep._ 1. By precipitating a solution of sulphate of quinine with a _slight_ excess of ammonia, potassa, or soda, and washing and drying the precipitate. By solution in alcohol, sp. gr. ·815, and spontaneous evaporation, it may be procured in crystals. Crystals may also be obtained from “its solution in hot water with a little ammonia.” (Liebig.)

2. (Direct.) By adding hydrate of lime, in slight excess, to a strong decoction of the ground bark made with water acidulated with sulphuric acid, washing the precipitate which ensues, and boiling it in alcohol; the solution, filtered while hot, deposits the alkaloid on cooling.

_Prop., &c._ Quinine, when prepared by precipitation, is an amorphous white powder, but when this precipitate is left in the liquor it assumes, after some time, the appearance of aggregated crystalline needles; when slowly crystallised from its solution, these needles are remarkably fine, and of a pearly or silky lustre. It is freely soluble in rectified spirit and in ether, and of all the cinchona-alkaloids it is the most soluble in ammonia. It is upon this fact that Kerner’s method for testing the purity of sulphate of quinine is founded. Its normal salts, if dissolved in water, have a slightly alkaline reaction upon red litmus paper. It is only sparingly soluble in water, even when boiling; both the fixed and volatile oils dissolve it with the aid of heat, more especially when it has been rendered anhydrous, or is presented to them under the form of an ethereal solution. It fuses by a gentle heat, without decomposition; forms crystallisable salts, which are only slightly soluble in water, unless it be acidulated, and, like the pure alkaloid, are extremely bitter, and possess much of the characteristic flavour of cinchona bark. It is precipitated by the alkalies and their carbonates, by tannic acid, and by most astringent substances.

_Pur._ See QUININE, SULPHATES OF, and QUINOMETRY (_below_).

_Tests._ Quinine is recognised by——1. Its appearance under the microscope.——2. Its solubility in ether, and in pure ammonia water.——3. Its solubility in concentrated nitric acid, forming a colourless liquid, which does not become yellowish until it is heated.——4. The solubility of itself and salts, when pure, in concentrated sulphuric acid, forming colourless fluids, “which do not acquire any coloration upon being heated to the point of incipient evaporation of the sulphuric acid, but which afterwards become yellow, and finally brown.” (Fresenius.)——5. Its solubility in concentrated sulphuric acid to which some nitric acid has been added, forming a colourless, or, at the most, only a faintly yellowish liquid.——6. It is wholly destroyed by heat.

A solution of quinine in acidulated water, and solutions of its salts, exhibit the following reactions:——1. Ammonia, potassa, and the alkaline carbonates, give white, pulverulent precipitates, becoming crystalline after some time (see _above_), and which are soluble in ammonia in excess, and which, when ether is added after the ammonia, and the whole is agitated, redissolve in the ether, whilst the clear liquid, on repose, presents two distinct layers.——2. Bicarbonate of soda (avoiding excess) gives a similar precipitate, both in acid and neutral solutions of quinine, either at once or after a short time. The precipitate is soluble in excess of the precipitant, and is again precipitated from the new solution upon protracted ebullition. “Vigorous stirring of the liquid promotes the separation of this precipitate.” (Fresenius.)——3. If recently prepared chlorine be added to it, and then ammonia, a beautiful emerald-green colour is developed. (Ph. L.)——4. A concentrated solution of ferrocyanide of potassium being added, in excess, after the chlorine, instead of the ammonia, a dark red colour is instantly produced, which after some time passes into green, especially when freely exposed to the light. This reaction is not characteristic of quinine, for with quinidine one gets the same reaction.——5. If caustic potassa be used instead of ammonia (see _above_), the solution acquires a sulphur-yellow colour. “These reactions are restricted to this alkaloid.” (Dr Garrod.)

Flückiger[126] says;——“The most characteristic test for ascertaining the presence of quinine is the formation of the splendid green compound called _thalleiochine_, which is produced if solutions of the alkaloid or its salts are mixed with chlorine water, and then a drop of ammonia added.”

[Footnote 126: In ‘Jahrb. f. Pharm.,’ April, 1872, 136 (‘Ph. Journ,’, 3rd series, ii, 901).]

If one part of quinine is dissolved in 4000 parts of acidulated water, and then about 1/10 of the volume of the liquid, of chlorine water, and a drop of ammonia added, a green zone will be readily formed if the liquids are cautiously placed in a flask without shaking.

If the solution of quinine contain no more than 1/5000, the green of one may still be obtained, but in more diluted solutions the success becomes more and more uncertain.

From a practical point of view we may state that 1/5000 of the alkaloid is the smallest quantity whose presence can thus be discovered with certainty; Kerner (1870) has succeeded with 1/20000 but I was not able to corroborate this statement.

The author was also induced to try the action of bromine in place of chlorine. The _thalleiochine_ is then, indeed, produced in solution which contain only 1/20000 of quinine.

Yet the behaviour of bromine displays some striking differences. Chlorine alone, as already stated, causes no immediate alteration of somewhat diluted solutions of quinine, whereas they became turbid on addition of bromine as long as there is about 1/2500 or more of quinine present. Now, the precipitate which is produced by bromine in solution of quinine does _not_ turn green if a little ammonia is subsequently added, or, at least, the thalleiochine thus obtained is rather greyish. But in more dilute solutions of quinine bromine acts more readily than chlorine. An excess of bromine is to be carefully avoided.

This is easily performed if the vapour of bromine, not the liquid bromine itself, is allowed to fall down on the surface of the solutions of quinine; their superficial layer only must be saturated with bromine by gently moving the liquid. Then a drop of ammonia will produce the green or somewhat bluish zone, which is much more persistent than that due to chlorine.

Consequently, for demonstration of the test under notice, chlorine is to be used in comparatively concentrated solutions. In solutions containing so little quinine (less than 1/2500) that it is no longer precipitated by the vapour of bromine, the thalleiochine test succeeds much better with bromine, and goes much further, as shown above.

The author also shows that morphine gives a dark, dingy brown colour with chlorine and ammonia, which is capable of more or less masking the reaction of quinine.

Another test for quinine is the formation of its iodosulphate, the so-called herapathite. For this purpose the quinine is dissolved in 10 parts of proof spirit, acidulated with 1/20th part of sulphuric acid, and to this solution an alcoholic solution of iodine is carefully added, and the liquid in the meanwhile stirred with a glass rod. There appears either immediately or after some minutes a black precipitate of iodosulphate of quinine, which if redissolved in boiling proof spirit, forms in cooling the beautiful crystals of herapathite. 100 parts of this herapathite, if dried on a water bath, represent 56·5 parts of pure quinine.

Dr de Vrij prefers the employment of the iodosulphate of chiniodine as a reagent for the detection and estimation of quinine. In a communication to the ‘Pharmaceutical Journal’ he writes:——“In estimating quinine in a mixture of cinchona-alkaloids by means of an alcoholic solution of iodine the reagent requires to be added in slight excess, in order to ensure complete precipitation. An undue excess of the reagent, however, causes the formation of a compound richer in iodine and much more soluble in alcohol than herapathite, and thus renders the determination inaccurate.”[127] For this reason the author suggests the application of an alcoholic solution of iodosulphate of chiniodine (so-called sulphate of amorphous quinine) in place of free iodine. The reagent is made as following:——

[Footnote 127: 3rd series, vi, 461.]

Two parts of sulphate of chiniodine are dissolved in eight parts of water containing 5 per cent. of sulphuric acid. To this _clear_ solution, contained in a large capsule, a solution of one part of iodine and two parts of iodide of potassium, in 100 parts of water, is _slowly_ added with continuous stirring, so that no part of the solution of chiniodine comes into contact with excess of iodine. By this addition an orange-coloured flocculent precipitate is formed of iodosulphate of chiniodine, which either spontaneously, or by a slight elevation of temperature, collapses into a dark brown, red-coloured, resinous substance, whilst the supernatant liquor becomes clear and slightly yellow coloured. This liquor is poured off, and the resinous substance is washed by heating it on a water bath with distilled water. After washing, the resinous substance is heated on the water bath till all the water has been evaporated. It is then soft and tenacious at the temperature of boiling water, but becomes hard and brittle after cooling. One part of this substance is now treated with 6 parts of alcohol of 92 or 94 per cent. until it is completely dissolved, and the solution allowed to cool. In cooling a part of the dissolved substance is separated. The clear dark-coloured solution is evaporated on a water bath, and the residue dissolved in 5 parts of cold alcohol. This second solution leaves a small part of insoluble substance. The clear dark-coloured solution obtained by the separation of this insoluble matter, either by decantation or filtration, constitutes the reagent which the author has used for some time under the name of iodosulphate of chiniodine, both for the qualitative and quantitative determination of _crystallisable_ quinine.

To determine a quantity of quinine contained in the mixed alkaloids obtained from a sample of cinchona bark, 1 part of the alkaloid is dissolved in 20 parts of alcohol, of 90 or 92 per cent., containing 1·6 per cent. of sulphuric acid, to obtain an alcoholic solution of the acid sulphates of the alkaloids.

From this solution the quinine is separated by adding carefully, by means of a pipette, the above-mentioned solution of the iodosulphate of chiniodine, as long as a dark brown-red precipitate of iodosulphate of quinine-herapathite is formed. As soon as all the quinine has been precipitated, and a slight excess of the reagent has been added, the liquor acquires an intense yellow colour. The beaker containing the liquor with the precipitate is now covered by a watch-glass, and heated on a water bath till the liquid _begins_ to boil.

After cooling, the beaker is weighed, to ascertain the amount of liquid which is necessary in order to be able to apply later the above-mentioned correction. For although quinine-herapathite is very little soluble in alcohol, it is not insoluble, and therefore a correction must be applied for the quantity which has been dissolved both by the alcohol used for the solution of the alkaloids and the alcohol contained in the reagents.

The liquor is now filtered to collect the iodosulphate of quinine on a small filter, where it is washed with a saturated solution of herapathite in alcohol. After the washing has been completed, the weight of the funnel with the moist filter is taken, and the filter allowed to dry in the funnel. As soon as it is dry the weight is taken again, to ascertain the amount of solution of herapathite which remained in the filter, and which left the dissolved herapathite on the filter after the evaporation of the alcohol.

This amount is subtracted from the total amount of liquid, and for the remaining the correction is calculated with reference to the temperature of the laboratory during the time of the analysis. The dry iodosulphate of quinine is taken from the filter and dried on a water bath, in one of a couple of large watch-glasses closing tightly upon each other, so that the weight of the substance contained in the glass may be taken without the access of air.

When, after repeatedly ascertaining the weight, it remains constant, this weight is noted down, and to it is added the product of the calculated correction. The sum of this addition is the total amount of iodosulphate of quinine obtained from the mixed alkaloids subjected to the operation, and from this weight the amount of _crystallisable_ quinine can be calculated by the use of Hauer’s formula, 2C_{40}H_{24}N_{2}O_{4}3(HO_{1}SO_{3}), 31 (old notation), which the author has found to be correct. According to this formula, 1 part of iodosulphate of quinine, dried at 100° C., represents 0·5509 per cent. of anhydrous quinine, or 0·7345 per cent. of disulphate of quinine.

The accuracy of this determination may be seen from the following examples:

0·24 gram of anhydrous crystallised quinine gave 0·541 gram of herapathite dried at 100° C. = 0·298 gram of quinine.

According to Hauer’s formula, 0·5336 gram of herapathite = 0·294 gram of quinine, which ought to have been obtained.

1·048 gram of bitartrate of quinine gave 1·224 gram of herapathite = 0·674 gram of quinine.

According to the formula of the bitartrate, C_{20}H_{24}N_{2}O_{21}C_{4}H_{6}O_{6} + Aq. = 442; 1·048 of bitartrate represents 0·69 of quinine, so that 1·255 gram of herapathite should have been obtained.

Notwithstanding the different circumstances in which the reagent was applied, the results are satisfactory.

The two following experiments were made with pure quinine, dried at 100° C., at which temperature it still retains water, under identical circumstances:——

1·0664 gram of hydrated quinine gave 1·7266 gram of herapathite = 164·5 per cent.

1·055 grams of the same hydrated quinine gave 1·7343 gram of herapathite = 164·3 per cent.

The author further states that the iodosulphate of quinine and of quinidine prepared by means of his new reagent have an analogous composition, and are identical with the compound described by Herapath, whilst the iodosulphates of cinchonine and cinchonidine have a different composition from the former, and both require more iodine to be converted into the optical iodosulphates described by Herapath. Of all these iodosulphates that of quinine is by far the most insoluble in alcohol, and is precipitated first and free from the others by a judicious application of the iodosulphate of chinioidine.

Quinine is distinguished from both cinchonine and quinidine by its comparatively free solubility in ether; the last of these being very sparingly soluble, and the other wholly insoluble, in that menstruum. The presence of cinchonine may also be positively determined by reference to the behaviour of that alkaloid. Quinidine is also distinguished from quinine by the different crystallisation, greater specific gravity, and freer solubility of its salts in cold water.[128]

[Footnote 128: An extremely elegant and highly sensitive method of testing for quinine and quinidine by means of the microscope, &c., is described at considerable length, by Dr Herapath, in the ‘Pharm. Journ.’ for November, 1853.]

_Estim._ See QUINOMETRY.

_Uses, &c._ Pure quinine is but rarely used in medicine, but several of its salts are employed as remedies, on account of their great stimulant, tonic, and febrifuge powers. As a tonic in dyspeptic affections, and for restoring strength and vigour to morbidly weakened habits, and as an antiperiodic or agent to counteract febrile action, it appears to be superior to all other remedies, provided no abnormal irritability of the mucous membranes, or of the circulatory organs, exists. The dose of the salts of quinine, as a tonic, is 1/2 to 1 gr., twice or thrice daily; as an antiperiodic, 2 to 5 gr., or even more, every second or third hour, during the intervals of the paroxysms of ague, and of other intermittent or periodic affections; also in acute rheumatism. The sulphate (disulphate) is the salt generally used; this and other salts are most effective when taken in solution.

The nature of the influence exerted upon blood by quinine was, in 1872, made the subject of a fresh investigation by Schulte.[129] Its extraordinary power of stopping fermentation and putrefaction, by destroying low organisms, such as bacteria and fungi, has been before pointed out. It is supposed to diminish the formation of pus in inflammation by arresting the motions and preventing the exit from the blood-vessels of the white blood-corpuscles, the accumulation of which, according to Cohnheim, constitutes pus.

[Footnote 129: ‘N. Rep. Pharm.,’ xx, 539 (‘Pharm. Journ.,’ 3rd series, ii, 629).]

By depriving the red blood-corpuscles of the power to produce ozone, it diminishes the change of tissue in the body, and thereby lessens the production of heat. Ranke and Kerner have shown the waste of tissue is reduced when large doses of quinine are administered, as indicated in the small proportion of uric acid and urea excreted.

With the object of ascertaining whether this effect is referable to the direct influence of quinine on oxidation in the blood, or to its indirect influence through the nervous system, Schulte employed a method, based upon the changes occurring in the alkalinity of the blood, observed by Zuntz, who had noticed that a considerable formation of acid takes place in freshly-drawn blood, and continues in a less degree till putrefaction commences.

The amount of acid formed was estimated from the diminished alkalinity of the blood, as comparatively shown by the quantity of dilute phosphoric acid required for exact saturation.

A sufficient quantity of chloride of sodium was added to the phosphoric acid to prevent the blood-corpuscles from being dissolved, and interfering with the reaction by their colouring matter. The point of saturation was fixed at the point of transient reddening of carefully prepared test paper by the carbonic acid. Schulte has thus been enabled to confirm the experiments of Zuntz and Scharrenbroich, showing that quinine and berberine lessen the production of acid, and that quinine can stop it both before and after coagulation; that sodium nitropicrate has an action similar to, and nearly as powerful as, quinine; while the action of cinchonine is much less energetic. Harley has shown that whilst quinine lessens oxidation in blood, some substances, such as snake poisons, increase it. Binz found that when putrid fluids were injected into the circulation of an animal, the temperature rose; but that this increase of temperature could be more or less prevented by the addition of quinine to the putrid liquid, or the simultaneous injection of the quinine.

With respect to the influences of quinine on the change of tissue, Schulte gives the result of some careful experiments made by Zuntz, who found that after taking three 0·6 gram doses of hydrochlorate of quinine for two days, the amount of urine he excreted was increased by one third, and then decreased as much, the specific gravity falling from 1018 to 1012; the urea also showed a marked decrease.

The salts of quinine may be made by simply saturating the dilute acids with the base, so that part of the latter remains undissolved, and gently evaporating the solutions for crystals, or to dryness. Prince Lucien Bonaparte recommends all these salts to be prepared by the addition of a strong alcoholic solution of quinine to a cold solution of the acid. We have tried this method with success.

=Quinine, Ac′etate of.= _Syn._ QUINÆ ACETAS, L. _Prep._ 1. (P. Cod.) Mix quinine, 2 parts, with water, 3 parts; heat the mixture, and add of acetic acid, q. s. to dissolve the alkaloid, and to render the solution slightly acid; lastly, decant or filter the solution whilst boiling hot, and set it aside to crystallise. The mother water, on evaporation, will yield a second crop of the acetate.

2. Effloresced sulphate of quinine, 17 parts, is dissolved in boiling water, and mixed with crystallised acetate of soda, 6 parts. The acetate of quinine crystallises.

_Prop., &c._ Satiny, acicular crystals, which are rather more soluble in water than those of the sulphate.——_Dose_, 1/2 to 5 grains.

=Quinine, Arse′′niate of.= _Syn._ QUINÆ ARSENIAS, L. _Prep._ (Bourières.) Arsenic acid, 1-1/2 dr.; quinine, 5 dr.; distilled water, 6 fl. oz.; boil them together in a covered glass vessel until the alkaloid is dissolved, then set the solution aside to crystallise.

_Uses, &c._ Recommended by Dr Neligan, and others, as being more powerfully antiperiodic than the other preparations of quinine.——_Dose_, 1/12 to 1/4 gr., made into pills; in agues, neuralgia, &c.; also in cancer.

=Quinine, Ar′senite of.= _Syn._ QUINÆ ARSENIS, L. _Prep._ Sulphate of quinine, 100 parts, is dissolved in alcohol, 600 parts, and boiled with arsenious acid, 14 parts. The liquid is then filtered. The poisonous salt is deposited in the crystalline form as the liquid cools.

_Uses, &c._ As the last.

=Quinine, Chlo′′ride of.= Hydrochlorate of quinine (see _below_).

=Quinine, Ci′trate of.= _Syn._ QUINÆ CITRAS, L. _Prep._ 1. By mixing a hot solution of sulphate of quinine with a like solution of citrate of soda.

2. From quinine and citric acid, as the acetate. Needle-shaped prisms.——_Dose, &c._ As the sulphate or disulphate.

=Quinine, Disulphate of.= Sulphate of quinine (see _below_).

=Quinine, Ferrocy′anide of.= _Syn._ CYANIDE OF IRON AND QUININE; QUINÆ HYDROFERROCYANAS, QUINÆ FERRO-PRUSSIAS, L. _Prep._ (P. Cod.) Sulphate of quinine, 100 parts; ferrocyanide of potassium, 31 parts; distilled water, 2500 parts; boil for a few minutes, and, when cold, separate the impure salt which floats as an oily mass on the surface, wash it with a little cold water, and dissolve it in boiling alcohol; the solution will deposit crystals as it cools.

_Obs._ This compound is by some said to be the most efficacious of all the salts of quinia. Pelouze asserts that it is simply quinine mixed with some Prussian blue.——_Dose_, 1 to 6 gr.

=Quinine, Ferrosul′phate of.= See QUININE AND IRON, SULPHATE OF (_below_).

=Quinine, Hydri′odate of.= _Syn._ IODIDE OF QUININE; QUINÆ HYDRIODAS, Q. IODIDUM, L. _Prep._ 1. By adding, drop by drop, a concentrated solution of iodide of potassium to a like solution of acid sulphate of quinine, and drying the precipitate in the shade; or heat the liquid nearly to the boiling point, and allow it to crystallise.

2. (Parrish.) Effloresced sulphate of quinine, 5 parts, dissolved in alcohol, and decomposed by an alcoholic solution of 3 parts of iodide of potassium, precipitates sulphate of potassa, and yields, on cooling and evaporating, hydriodate of quinine in fine crystalline needles.[130]

[Footnote 130: “1 and 2 are not identical; 1 is an acid salt which readily crystallises, but 2 is a normal salt which I never saw crystallise, but always like a fluid resin, quite amorphous.”——De Vrij.]

3. (IODURETTED——Bouchardat.) From an acid solution of quinia and a solution of iodide of iron containing a slight excess of iron, as No. 1.

_Obs._ The above are reputed alterative, tonic, and antiperiodic.——_Dose_, 1 to 4 gr.; in obstinate intermittents, and in the scrofulous affections of debilitated subjects.

=Quinine, Hydrochlo′′rate of.= _Syn._ CHLORIDE OF QUININE, MURIATE OF QUININE†; QUINÆ HYDROCHLORAS, QUINÆ MURIAS, L. _Prep._ 1. By neutralising dilute hydrochloric acid with the base, as above.

2. (Ph. Bor.) Chloride of barium, 5 dr.; boiling water, 1 lb.; dissolve, add, gradually, of sulphate of quinine, 2 oz.; boil gently for a few minutes, filter the solution whilst hot, and set it aside that crystals may form.

3. (QUINÆ MURIAS——Ph. D.) Dissolve chloride of barium, 123 gr., in distilled water, 2 fl. oz.; add of sulphate of quinine, 1 oz., dissolved in boiling water, 1-1/2 pint; mix, evaporate the solution to one half, filter, and again evaporate until spiculæ begin to appear; next allow the liquid to cool, collect the crystals, and dry them on bibulous paper. The mother liquor, by further concentration and cooling, will yield an additional product.

_Obs._ Hydrochlorate of quinine occurs in snow-white groups of feathery crystals, of a mother-of-pearl lustre, which are more freely soluble than those of the disulphate.

=Quinine and Iodide of Iron.= _Syn._ QUINÆ ET FERRI IODIDUM. (Bouchardat.) _Prep._ Pour a strong solution of acid sulphate of quinine into a fresh solution of iodide of iron; collect the precipitate, dry it quickly by pressing it between blotting paper, and keep it from the air.

=Quinine, Ki′nate of.= _Syn._ QUINÆ KINAS, L. _Prep._ By saturating a solution of kinic acid with quinine, and purifying by crystallisation out of alcohol. The kinate of quinine is obtained in crystalline warts, soluble in 4 parts of water and 8 parts of alcohol.

=Quinine, Lac′tate of.= _Syn._ QUINÆ LACTAS, L. _Prep._ As the ACETATE or CITRATE. By spontaneous evaporation fine crystals may be obtained. Said to agree better with dyspeptic patients than the other salts of quinine.

=Quinine, Mu′′riate of.= Hydrochlorate of quinine (see _above_).

=Quinine, Neutral Hydrobromate of.= _Syn._ QUINÆ HYDROBROMAS. (M. Boille.) This salt is prepared by double decomposition of bromide of barium and neutral sulphate of quinia, and is thus easily obtained pure and free from chloride, the great solubility of bromide of barium in alcohol facilitating the removal of any chloride which is insoluble.

The two salts are dissolved separately in alcohol and the solutions filtered. The neutral sulphate of quinia solution is gradually added, in slight excess, to the bromide of barium solution until a precipitate ceases to form.

The solutions, diluted with water, are distilled to recover the alcohol, afterwards filtered to separate the sulphate of quinia which has been precipitated by the water, and then concentrated sufficiently to induce rapid crystallisation. The addition of water is indispensable for the concentration and crystallisation; the hydrobromate, being soluble in alcohol of all proportions, redissolves as the alcoholic liquor is concentrated. M. Boille claims for his neutral hydrobromate of quinine its much readier solubility over the officinal sulphate, as well as its superior richness in quinine.

=Quinine, Ni′trate of.= _Syn._ QUINÆ NITRAS, L. _Prep._ As the HYDROCHLORATE, substituting dilute nitric acid, or nitrate of baryta (P. Cod.), for hydrochloric acid or chloride of barium.

=Quinine, Phos′phate of.= _Syn._ QUINÆ PHOSPHAS, L. As the ACETATE. Silky, needle-shaped crystals, with a pearly lustre. It has been highly recommended in intermittents, &c., associated with rickets and stomach affections.

=Quinine, Salicylate of.= _Syn._ QUINÆ SALICYLAS. This may be made by mixing an alcoholic solution of quinine with an alcoholic solution of salicylic acid to complete saturation, and afterwards allowing the alcohol slowly to evaporate.

=Quinine, Sul′phates of.= The salt often called ‘disulphate of quinine’ is now generally regarded as the normal sulphate, while the soluble salt, often called the ‘neutral sulphate’ is considered to be an acid salt. This change in nomenclature results from doubling the atomic weight of the alkaloid quinine:——

1. =Quinine Acid, Sulphate of.= (C_{20}P_{24}N_{3}O_{2}.H_{2}SO_{4}.7Aq.) _Syn._ SULPHATE OF QUININE†, NEUTRAL SULPHATE OF QUININE†, SOLUBLE S. OF Q.; QUINÆ SULPHAS SOLUBILIS, L. _Prep._ From sulphate of quinine, 1 oz., dissolved, by the aid of heat, in water, 1/2 pint, previously acidulated with dilute sulphuric acid, 5 fl. dr.; the solution affords crystals on cooling, and more on evaporation.

_Obs._ This salt possesses the advantage of being soluble in about 10 parts of water at 60° Fahr.; but it is seldom used in the crystalline form; still, as the officinal sulphate (‘disulphate’) is generally prescribed along with a small quantity of dilute sulphuric acid to render it soluble, this acid sulphate is, in fact, the compound which is commonly given. It is the ‘bisulphate,’ ‘supersulphate,’ or ‘acid sulphate of quina’ of Soubeiran and other Continental chemists.

2. =Quinine, Sulphate of.= (C_{20}H_{24}N_{2}O_{2})_{2}.2H_{2}SO_{4}.7Aq. _Syn._ NORMAL SULPHATE OF QUININE, DISULPHATE OF Q., QUININE; QUINÆ DISULPHAS (Ph. L.), QUINÆ SULPHAS (Ph. E., D., & U. S., & P. Cod.), QUINÆ SULPHAS (B. P.), L.; SULPHATE DE QUININE, Fr. _Prep._ 1. (Ph. L. 1836.) Take of yellow cinchona bark, bruised, 7 lbs.; sulphuric acid, 4-1/4 oz.; (diluted with) water, 6 galls.; boil them for 1 hour, and strain; repeat this a second time for 1 hour, with a like quantity of acid and water, and again strain; next boil the bark for 3 hours, in water, 8 galls., and strain; wash the residue with fresh quantities of boiling distilled water; to the mixed decoctions and washings, add moist hydrated oxide of lead to saturation, decant the supernatant fluid, and wash the sediment with distilled water; boil down the liquor for 15 minutes, and strain, then precipitate the quina with liquor of ammonia and wash the precipitate (with very cold water) until nothing alkaline is perceptible; saturate what remains with sulphuric acid, 1/2 oz., diluted with water, q. s., digest with animal charcoal, 2 oz., and strain; lastly, the charcoal being well washed, evaporate the mixed liquors, that crystals may form.

2. (Ph. E.) This process varies from the last one, in the bark (1 lb.) being first boiled in water (4 pints) along with carbonate of soda (4 oz.); the residuum, being pressed, is moistened with water, and again pressed, and this operation is repeated a second and a third time, the object being to remove, as much as possible, the acids, colouring matter, gum, and extractive, before proceeding to extract the alkaloid. Carbonate of soda is also used as the precipitant, instead of ammonia, and the precipitate is formed into a sulphate (disulphate) by being stirred with boiling water, 1 pint, to which sulphuric acid, 1 fl. scruple, or q. s., is subsequently added. The crystals, after digestion with prepared animal charcoal, 2 dr., are ordered to be dried at a heat not higher than 140° Fahr.

3. (Ph. D.) Yellow bark, 1 lb., is macerated for 24 hours in water, 2 quarts, acidulated with oil of vitriol, 2 fl. dr., and then boiled for half an hour, after which the fluid is decanted; this is repeated a second and a third time with water, 2 quarts, and oil of vitriol, 1 fl. dr.; the decanted (or strained) liquors are evaporated to a quart, and filtered, and slaked lime, 1 oz., or q. s., added to the solution until it exhibits a decidedly alkaline reaction; the precipitate is next collected on a calico filter, and, after having been washed with cold water, partially dried on porous bricks, and subjected to powerful pressure enveloped in blotting paper, is boiled for 20 minutes in rectified spirit, 1 pint, and the liquid, after subsidence, decanted; this is repeated a second and a third time with a fresh pint of spirit, and the residuum being well pressed, the mixed liquors are filtered, and the spirit removed by distillation; the brown viscid residuum is dissolved in boiling water, 16 fl. oz., boiled, and dilute sulphuric acid, 1/2 fl. oz, or q. s., added to render the solution neutral or only slightly acid; animal charcoal, 1/2 oz., is next stirred in, the mixture boiled for about 5 minutes, filtered, and set aside to crystallise; the crystals are dried on blotting paper by mere exposure to a dry atmosphere.

4. (B. P.) Yellow cinchona bark, in coarse powder, 16; hydrochloric acid, 3; distilled water, a sufficiency; solution of soda, 80; dilute sulphuric acid, a sufficiency. Dilute the hydrochloric acid with 10 pints of the water. Place the bark in a porcelain basin, and add to it as much of the diluted hydrochloric acid as will render it thoroughly moist. After maceration, with occasional stirring, for twenty-four hours, place the bark in a displacement apparatus, and percolate with the diluted hydrochloric acid until the solution which drops through is nearly destitute of bitter taste. Into this liquid (hydrochlorate of quinine) pour the solution of soda, agitate well, let the precipitate (quinine) completely subside, decant the supernatant fluid, collect the precipitate on a filter, and wash it with cold distilled water until the washings cease to have colour. Transfer the precipitate to a porcelain dish containing a pint of distilled water, and, applying to this the heat of a water bath, gradually add diluted sulphuric acid until very nearly the whole of the precipitate has been dissolved, and a neutral liquid has been obtained. (Or add about half the precipitated quinine to some water in an evaporating basin, warm the mixture and pour in diluted sulphuric acid until the precipitate has dissolved and the liquid is neutral or only faintly acid, then add the other half, stir well, and again heat liquid.) Filter the solution (sulphate of quinine), while hot, through paper, wash the filter with boiling distilled water, concentrate till a film forms on the surface of the solution, and set it aside to crystallise. The crystals should be dried on filtering paper without the application of heat.

5. “Those who are well acquainted with the chemistry of the cinchona-alkaloids all agree with me in condemning the boiling of bark with dilute acids. I prefer the following method, which can also be used on a small scale for quinometry:——

“Yellow bark, or any other bark in which quinine prevails, like, for instance, that of _Cinchona officinalis_, 1 lb., is mixed with milk of lime, made from 4 oz. of lime and 40 oz. of water. After drying this mixture it is exhausted with strong methylated spirit (the strongest possible) and the slightly coloured solution neutralised with sulphuric acid, so that the liquor has a slight acid reaction upon blue litmus paper. After filtering or subsiding, the clear liquid is distilled and the residue in the still dissolved in water, carefully neutralised, so that the solution has a slight alkaline reaction upon red litmus paper, treated with charcoal and crystallised, &c.”——De Vrij.

6. (‘HOSPITAL SULPHATE’——Mr E. Herring.) The crushed bark is boiled in a solution of caustic soda or potassa, to extract colouring matter and gum; it is then pressed, washed with cold water, a second time boiled with a solution of caustic alkali, and again pressed, washed, and pressed; the decoloured and purified bark is next exhausted by coction with acidulated water, in the usual way, and the filtered mixed decoctions are precipitated with carbonate of soda; the precipitated quina is then dissolved in hot dilute sulphuric acid, to saturation, when the ‘HOSPITAL SULPHATE’ crystallises out as the solution cools; this is, lastly, washed with a little cold water, drained, and dried.——The advantage of this process is the non-use of animal charcoal as a bleacher, and the consequent less cost of the product. In the preparation of his ‘WHITE SULPHATE,’ Mr Herring uses benzol as a solvent, instead of alcohol. Patent dated July 28th, 1853.

_Prop._ When pure, sulphate of quinine forms very light, delicate, flexible, white needles, which are efflorescent, inodorous, and intensely bitter; it is soluble in 740 parts of water at 60°, and in 30 parts at 212° Fahr.; it takes about 80 parts of cold rectified spirit for its solution, but is freely soluble in boiling alcohol and in acidulated water; it melts at 240° Fahr., and is charred and destroyed at a heat below that of redness. The crystals contain 76·1% of quinine, 8·7% of sulphuric acid, and 15·2% of water; of the last, they lose about 3-4ths by exposure to dry air, and nearly the whole when kept in a state of fusion for some time.

_Pur._ This may not be inferred from the form of its crystallisation, for the sulphates of quinidine and of cinchonidine may be obtained in the same form of crystallisation. As mentioned already, the reaction with chlorine and ammonia does not distinguish quinine from quinidine, as both give the same green colour. “It is entirely soluble in water (hot), and more readily so when an acid is present. Precipitated by ammonia, the residuary liquid, after evaporation, should not taste of sugar. By a gentle heat it loses 8% or 10% of water. It is wholly consumed by heat. If chlorine be first added, and then ammonia, it becomes green.” (Ph. L. 1836.) “On adding chloride of barium to 100 gr. of this salt, dissolved in water mixed with hydrochloric acid, 26·6 gr. of sulphate of baryta, dried at a red heat, are prepared.” (Ph. L. 1851.) “A solution of 10 gr., in 1 fl. oz. of distilled water, and 2 or 3 drops of sulphuric acid, if decomposed by a solution of 1/2 oz. of carbonate of soda, in two waters, and heated until the precipitate shrinks and fuses, yields, on cooling, a solid mass, which, when dry, weighs 7·4 gr. and when reduced to powder, dissolves entirely in a solution of oxalic acid.” (Ph. E.)

_Adult._ Sulphate of quinine is said to be often adulterated with starch, magnesia, gum, sugar, cinchonine, quinidine, &c.; but, according to De Vrij, those with starch, magnesia, gum, and sugar, are very rare if ever they were really observed. Very frequent are those with the sulphates of the other cinchona-alkaloids, and these become even still more frequent, as very different kinds of bark are used for the manufacture of quinine. Salicin is, if ever, but very seldom used for adulteration of quinine. The best practical test for the purity of sulphate of quinine is the following:——A saturated solution of the salt is made at 60° Fahr., and one part of this solution is mixed with 2 or 3 minims of a concentrated solution of iodide of potassium, whilst another part is mixed with 2 or 3 minims of a concentrated solution of tartrate of potash and soda. If the sulphate of quinine is pure its solution will remain unaltered by both reagents, even after rubbing the sides of the test tube with a glass rod and standing many hours. But if it contains one or more of the other cinchona-alkaloids there will appear either precipitates or striæ on the glass where it has been rubbed by the glass rod. Iodide of potassium indicates particularly the presence of even traces of quinidine, but also of cinchonidine and cinchonine, provided their quantity be not too small. Tartrate of potash and soda indicate, under these circumstances, only the presence of cinchonidine. The first three remain undissolved when the salt is digested in spirit; the fourth is dissolved out by cold water; the fifth may be detected by its total insolubility in ether; or, by precipitating the quinine by solution of potassa, and dissolving the precipitate in boiling alcohol; cinchonine crystallises out as the solution cools, but the quinine remains in the mother liquor; and the last, by the greater solubility and sp. gr. of the salt, &c. If the sample disengages ammoniacal fumes when treated with liquor of potassa, it contains sal ammoniac. The presence of most foreign organic substances is also shown by the sample being turned brown, and being soon charred when treated with a drop of concentrated sulphuric acid. If it turn red it contains salicin, a substance which is now frequently used to adulterate sulphate of quinine. The pure sulphate is not discoloured by this reagent.

_Uses, &c._ The sulphate is more extensively employed than any of the other salts of quinine, and, indeed, to almost the exclusion of them. It is the article intended to be used whenever ‘sulphate’ or ‘disulphate’ of quinine, or even ‘quinine,’ is ordered for medicinal purposes, unless the name is qualified by some other term. It is a most valuable stomachic, in doses of 1/4 to 1 gr.; as a tonic, 1 to 3 gr.; and as a febrifuge, 2 to 20 gr.

=Quinine, Sulpho-tar′trate of.= _Syn._ QUINÆ SULPHO-TARTRAS, L. _Prep._ From sulphate of quinine, 4 parts; tartaric acid, 5 parts; distilled water, 20 parts; mix, gently evaporate to dryness, and powder the residuum.

=Quinine, Tan′nate of.= _Syn._ QUINÆ TANNAS, L. _Prep._ Dissolve sulphate of quinine in slightly acidulated water, and add a solution of tannic acid as long as a precipitate forms; wash this with a little cold water, and dry it. The Ph. Græca orders infusion of galls to be used as the precipitant. In intermittent neuralgia.

=Quinine, Tar′trate of.= _Syn._ QUINÆ TARTRAS, L. _Prep._ (P. Cod.) From tartaric acid and quinine, as the acetate.

=Quinine, Vale′′rianate of.= _Syn._ QUINÆ VALERIANAS (Ph. D.), L. _Prep._ 1. As the acetate or citrate.

2. (Ph. D.) Valerianate of soda, 124 gr., distilled water, 2 fl. oz.; dissolve; also dissolve hydrochlorate of quinine, 7 dr., in distilled water, 14 fl. oz.; next heat each solution to 120° (not higher), mix them, and set the vessel aside for 24 hours; lastly, press the mass of crystals thus obtained, and dry them, without the application of artificial heat.

_Prop., &c._ Silky needles and prisms; its solution suffers decomposition when heated much above 120° Fahr. It is powerfully antispasmodic, antiperiodic, and nervine.——_Dose_, 1/2 gr., every two hours, or 1 to 3 gr. twice or thrice daily; in epilepsy, hemicrania, hysteria, neuralgia, and other nervous affections.

=QUININE AND COD-LIVER OIL.= _Syn._ COD-LIVER OIL WITH QUININE, QUINIARETTED COD-LIVER OIL; OLEUM MORRHUÆ CUM QUINÂ, OLEUM JECORIS ASELLI CUM QUINÂ, L. This medicine is a solution of pure anhydrous quinine in pure cod-liver oil.

_Prep._ 1. Pure quinine (preferably recently precipitated) is fused in a glass or porcelain capsule by the heat of an oil or sand bath, carefully applied, by which it assumes a brown colour and the appearance of a resin; it is then allowed to cool out of contact with the air, after which it is reduced to powder in a dry mortar, and added to pure pale Newfoundland cod-liver oil, gently heated in a closed glass vessel over a water bath; the solution of the alkaloid is promoted by constant agitation, and, when complete, the vessel, still corked, is set aside in a dark situation to cool; when the ‘quiniaretted oil’ is quite cold it is put into bottles, in the usual manner, and preserved as much as possible from the light and air.

2. The anhydrous quinine is dissolved in a little anhydrous ether before adding it to the oil, which in this case need not be heated, as the union is effected by simple agitation; should this not take place, it may be gently warmed for a few minutes.

3. The anhydrous quinine is dissolved in anhydrous alcohol, and after being added to the oil, the whole is gently heated, in an open vessel, by the heat of a water bath, until the alcohol is expelled; agitation, &c., being had recourse to as in No. 1.

_Prop., &c._ The above preparation resembles ordinary cod-liver oil, except in having a pale yellowish colour and a slightly bitter taste, similar to that of cinchona bark. It is said to possess all the properties of cod-liver oil combined with those peculiar to quinine, by which the tonic, stomachic, and antiperiodic qualities of the latter are associated, in one remedy, with the genial supporting, and alterative action of the other. The common strength is 2 gr. of quinine per oz.

=QUININE AND I′RON.= These two important medicinal agents are combined together in various ways. The following compound salts are often prescribed.