Cooley's Cyclopaedia of Practical Receipts Volume Ii Part 184

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 gla.s.s 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 565 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 pota.s.sium, 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, const.i.tutes the reagent which the author has used for some time under the name of iodosulphate of chiniodine, both for the qualitative and quant.i.tative determination of _crystallisable_ quinine.

To determine a quant.i.ty 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 16 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-gla.s.s, 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 quant.i.ty 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 a.n.a.lysis. The dry iodosulphate of quinine is taken from the filter and dried on a water bath, in one of a couple of large watch-gla.s.ses closing tightly upon each other, so that the weight of the substance contained in the gla.s.s 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 05509 per cent. of anhydrous quinine, or 07345 per cent. of disulphate of quinine.

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

024 gram of anhydrous crystallised quinine gave 0541 gram of herapathite dried at 100 C. = 0298 gram of quinine.

According to Hauer's formula, 05336 gram of herapathite = 0294 gram of quinine, which ought to have been obtained.

1048 gram of bitartrate of quinine gave 1224 gram of herapathite = 0674 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; 1048 of bitartrate represents 069 of quinine, so that 1255 gram of herapathite should have been obtained.

Notwithstanding the different circ.u.mstances 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 circ.u.mstances:--

10664 gram of hydrated quinine gave 17266 gram of herapathite = 1645 per cent.

1055 grams of the same hydrated quinine gave 17343 gram of herapathite = 1643 per cent.

The author further states that the iodosulphate of quinine and of quinidine prepared by means of his new reagent have an a.n.a.logous 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 acc.u.mulation of which, according to Cohnheim, const.i.tutes 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 quant.i.ty of dilute phosphoric acid required for exact saturation.

A sufficient quant.i.ty 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 06 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._ QUINae 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, a.r.s.e"niate of.= _Syn._ QUINae a.r.s.eNIAS, L. _Prep._ (Bourieres.) a.r.s.enic acid, 1-1/2 dr.; quinine, 5 dr.; distilled water, 6 fl. oz.; boil them together in a covered gla.s.s 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._ QUINae a.r.s.eNIS, L. _Prep._ Sulphate of quinine, 100 parts, is dissolved in alcohol, 600 parts, and boiled with a.r.s.enious 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._ QUINae 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; QUINae HYDROFERROCYANAS, QUINae FERRO-PRUSSIAS, L. _Prep._ (P. Cod.) Sulphate of quinine, 100 parts; ferrocyanide of pota.s.sium, 31 parts; distilled water, 2500 parts; boil for a few minutes, and, when cold, separate the impure salt which floats as an oily ma.s.s 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 a.s.serts 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_).