Quininae Sulphas, B.P. Quinine Sulphate.
C80H100N8O16S2, 15H2O = 1763.26.
Quinine sulphate, [(C20H24N2O2)2H2SO4]2, 15H2O, may be prepared by mixing the finely powdered bark with milk of lime, and exhausting the mixture with hot kerosene, or other solvent, from which, after concentration, the alkaloids are extracted as acid sulphates by means of diluted sulphuric acid. The acid solution is treated with animal charcoal, filtered while hot, and neutralised with solution of sodium hydroxide, when, on cooling, neutral quinine sulphate crystallises out, separating from the other sulphates which are more soluble, and consequently remain in the mother-liquor. The quinine sulphate is purified by recrystallisation. The salt contains 73.55 per cent. of anhydrous quinine, 11.12 per cent. of sulphuric acid, and 15.32 per cent. of water of crystallisation. Quinine sulphate is also official in the U.S.P. where the formula is given as (C20H24N2O2)2, H2SO4, 7H2O. It occurs in the form of odourless, white, flexible, silky, filiform crystals, having a persistent and intensely bitter taste; efflorescent on exposure to dry air, becoming lustreless and acquiring a brownish tint on exposure to light. It may be either light or heavy according to the method of manufacture, but in either case it forms an easily compressible mass. The aqueous solutions of quinine sulphate are neutral and fluorescent, and when treated with solution of bromine or chlorine, and then sciatica of ammonia, yield the characteristic emerald-green colour, or thalleioquin reaction, and this on further treatment with mineral acids changes to red; with alkalies and their carbonates the alkaloid is precipitated, but in the case of ammonia is redissolved by excess; tannic acid forms an insoluble tannate. The fluorescence of the aqueous solution is intensified by the addition of diluted sulphuric acid. In dry air the salt effloresces and loses part of its writer of crystallisation, the remaining salt containing two molecules of water to each molecule of sulphate. At 100°, the salt becomes anhydrous, and when exposed to the air again takes up two molecules of water, so that a perfectly stable salt (C20H24N2O2)2, H2SO4, 2H2O results. It melts at 205° when dried over sulphuric acid. On ignition, it burns without leaving any residue (absence of mineral impurities). Concentrated sulphuric acid should not produce more than a faintly yellow colour (limit of readily carbonisable impurities), and nitric acid should not produce a red colour (difference from morphine). The impurity most frequently present in quinine sulphate is cinchonidine sulphate, resulting from imperfect separation in the process of manufacture. Commercial quinine sulphate, however, may be obtained practically free from cinchonidine. This and other cinchona alkaloids should be tested for in the following way:—Dry 2 grammes of the salt at 50° for two hours in a porcelain dish on a water-bath. The residue, which must be perfectly neutral, is transferred to a dry test-tube, and 20 mils of water added. It is then heated on a water-bath for half an hour at 65°, allowed to cool to 15°, at which temperature it is kept for two hours with occasional shaking. The solution is then filtered, 5 mils of the filtrate being transferred to a dry test-tube, and solution of ammonia carefully added from a burette until the precipitate just redissolves; not more than 6 mils of solution of ammonia should be required to produce a clear solution. The temperature of the liquids must be at 150. A clear solution indicates absence of excessive amounts of other cinchona alkaloids. The pink colouring of quinine issued from Government factories in India is intended merely to distinguish quinine manufactured by Government from ordinary commercial quinine and to prevent fraud.
Soluble in water (about 1 in 800), boiling water (1 in 25), alcohol (1 in 65), boiling alcohol (1 in 6); almost insoluble in ether or chloroform; easily soluble in a mixture of 2 parts of chloroform and 1 part of absolute alcohol; diluted acids increase its solubility in water.
Action and Uses.—Quinine sulphate is the most commonly used salt of quinine, though for general purposes the hydrochloride is preferable (see Quininae Hydrochloridum). One grain of quinine sulphate is rendered soluble by 1 minim of diluted sulphuric or nitric acid, or 2 minims of diluted phosphoric acid; the acid should in each case be diluted with from six to ten times its bulk of water before adding the quinine salt. For the general properties of the salts of quinine see Quinina. Large doses are given in malarial and intermittent fevers, smaller doses in continued fevers, neuralgia, and as a tonic, to improve the appetite. For external use, solutions (1 in 200) are employed, with a spray or nasal douche in bay fever; for corneal ulcers 1 in 500 is used and the salt dissolved with a minimum of diluted sulphuric acid, or preferably the acid sulphate is employed. Quinine sulphate may be administered mixed with milk, or in cachets, pills, or mixture. The B.P. pill contains tartaric acid to assist solution of the alkaloid in the stomach; quinine pills may also be prepared with syrup of glucose. If the bitterness of quinine in solution be objectionable, the alkaloidal salt may be suspended in water with the aid of Pulvis Tragacanthae Compositus. It dissolves readily in tincture of ferric chloride, and is frequently so prescribed. Quinine sulphate is incompatible with alkalies and their carbonates (e.g., Spiritus Ammoniae Aromaticus), benzoates, salicylates, iodides, tannic acid, and mercuric chloride. These substances precipitate the alkaloid or form insoluble salts, which become adherent to the sides of the bottle; the addition of mucilage of gum acacia usually keeps the precipitated alkaloid in a diffusible condition. When reacting salts are present in quinine mixtures, the salt should be added in as dilute solution as possible to the quinine solution, also diluted, containing the mucilage. Mixtures of sodium salicylate with quinine should contain no free acid; the quinine salt should be suspended with a little mucilage and the sodium salicylate added in solution. Effervescent mixtures of acid and alkaline solutions should contain the quinine in the acid portion. For hypodermic use the acid hydrobromide and acid hydrochloride are preferred. Ammoniated tincture of quinine is largely employed; when it is diluted with water the quinine is thrown out of solution, and mucilage should be added to the mixture to retain the precipitate in a diffusible condition. If the tincture be poured into aerated water or hot water, the alkaloid is not so readily thrown out of solution.
Dose.—½ to 6 decigrams (1 to 10 grains).
- Elixir Quininae Ammoniatum, B.P.C.—AMMONIATED ELIXIR OF QUININE.
- This elixir is a more palatable preparation than ammoniated tincture of quinine, and contains one-half the amount of quinine sulphate, with flavouring agents. It is used for influenza and catarrh. Dose.—2 to 8 mils (½ to 2 fluid drachms).
- Elixir Quininae Ammoniatum Compositum, B.P.C.—COMPOUND AMMONIATED ELIXIR OF QUININE.
- This preparation contains the same amount of quinine sulphate as ammoniated tincture of quinine, and is used for similar purposes. Dose.—2 to 4 mils (½ to 1 fluid drachm).
- Liquor Quininae et Strychninae, B.P.C.—SOLUTION OF QUININE AND STRYCHNINE. Syn.—Liquor pro Syrupo Eastoni.
- This solution contains 34 grains of quinine sulphate, 1 ⅓ grains of strychnine, and 16 minims of concentrated phosphoric acid in 1 fluid ounce. It is used for the extemporaneous production of Syrupus Ferri Phosphatis cum Quinina et Strychnina, 1 ½ volumes of the solution being mixed with 1 of solution of ferrous phosphate and a sufficient syrup to produce 8 by volume.
- Mistura Quininae, B.P.C.—QUININE MIXTURE.
- Each fluid ounce contains 1 grain of quinine sulphate, 1 minim of diluted sulphuric acid, and 10 minims of tincture of orange. This mixture is employed as a simple bitter to stimulate gastric secretion by improving the appetite; it is of value in the debility following acute illness. Dose.—15 to 30 mils (½ to 1 fluid ounce).
- Mistura Quininae cum Ferro, B.P.C.—QUININE MIXTURE WITH IRON.
- Each fluid ounce contains 1 grain of quinine sulphate, and 10 minims of solution of ferric chloride. This is a convenient way of prescribing quinine and iron together. Dose.—15 to 30 mils (½ to 1 fluid ounce).
- Pilula Quininae Sulphatis, B.P.—PILL OF QUININE SULPHATE.
- Quinine sulphate, 30; tartaric acid, 1; glycerin, by weight, 4: tragacanth, in powder, 1. Twelve centigrams (2 grains) of this pill mass contains about 1 ⅔ grains of quinine sulphate. Dose.—12 to 48 centigrams (2 to 8 grains).
- Pilulae Quininae cum Ferro, B.P.C.—QUININE PILLS WITH IRON.
- Each pill contains 1 grain each of quinine sulphate and exsiccated ferrous sulphate. Dose.—1 or 2 pills.
- Pilulae Quininae Sulphatis Compositae, B.P.C.—COMPOUND QUININE SULPHATE PILLS. Syn.—Aitkin's Tonic Pills.
- Each pill contains ½ grain of quinine sulphate, ⅓ grain of reduced iron, 1/100 grain of arsenious anhydride, 1/100 grain of strychnine, with a sufficient quantity of extract of gentian. Dose.—1 or 2 pills.
- Tablettae Quininae B.P.C.—QUININE TABLETS. 1 grain.
- Dose.—1 or 2 tablets. Larger tablets containing 12 or 30 centigrams (2 or 5 grains) of quinine sulphate, are sometimes required.
- Tablettae Quininae et Ferri, B.P.C.—QUININE AND IRON TABLETS. Syn.—Tablettae Quininae cum Ferro.
- Each tablet contains 1 grain of quinine sulphate and 1 grain of exsiccated ferrous sulphate. Dose.—1 to 3 tablets.
- Tinctura Quininae Ammoniata, B.P.—AMMONIATED TINCTURE OF QUININE.
- Quinine sulphate, 2; solution of ammonia, 10; alcohol (60 per cent.), 90. Diffuse the quinine in the alcohol, add the solution of ammonia, shake until solution is effected, and filter. The deposit sometimes found in this tincture consists of cinchonidine sulphate, present as an impurity in the quinine sulphate. This preparation is a popular remedy for colds. It has the combined action of small doses of quinine and ammonia. Mixtures containing ammoniated tincture of quinine require the addition of one sixteenth to one-eighth of their bulk of mucilage of gum acacia, according to the amount of tincture present. Dose.—2 to 4 mils (½ to 1 fluid drachm).