C. Quinidine
Synonyms Conquinine; Pitayine; b-Quinine;
Biological Source Quinidine is obtained from the various species of Cinchona as described under quinine (section ‘A’). It is reported to be present in cinchona barks ranging between 0.25-3.0%.
Chemical Structure It is the dextrorotatory stereoisonter of quinine
(9S)-6′-Methoxycinchonan-9-ol; (C20H24N2O2).
Isolation Quinidine may be isolated from the cinchona bark by the method stated under quinine (section ‘A’).
Characteristic Features
1. Quinidine is obtained as triboluminescent crystals having mp 174-175°C after drying of the solvated crystals.
2. Its specific optical rotations are: [α]15D + 230° (C = 1.8 in chloroform); [α]17D + 258° (ethanol); and [α]17D + 322° (C = 1.6 in 2m HCl).
3. It has two dissociation constants, namely: pK1 (20°) 5.4; and pK2 10.0.
4. It gives a distinct and characteristic blue fluorescence in dilute sulphuric acid (2N).
5. The uv absorption spectrum is identical with that of quinine.
6. Solubility Profile: 1 g gets dissolved in 2000 ml cold water, 800 ml boiling water, 36 ml ethanol, 56 ml ether, 1.6 ml chloroform; very soluble in methanol; and practically insoluble in petroleum ether.
Identification Tests The various derivatives of quinidine have specific characteristic features as enumerated below:
1. Quinidine Sulphate Dihydrate [(C20H24N2O2)2.H2SO4.2H2O] (Synonyms Quinidex; Quinicardine; Quinora; Extentabs; Cin-Quin): It is mostly obtained as white, very bitter, odorless, fine crystals which is frequently cohering in masses. It does not lose all of its water of crystallization below 120°C. It has been found to darken on exposure to light. It has [α]25D ~ + 212° (in 95% ethanol); and ~ + 260° (in dilute HCl). The pH of a 1% (w/v) solution between 6.0-6.8. Its pKa values are : 4.2 and 8.8. 1 g dissolves in 90 ml water, 15 ml boiling water, 10 ml ethanol, 3 ml methanol, 12 ml chloroform; and insoluble in ether and benzene.
Note: Quinidine sulphate dihydrate is the salt of an alkaloid obtained either from various species of Cinchona and their hybrids, or from Cuprea bark, obtained from Remijia pedunculata and Remijia purdieana belonging to the natural order Rubiaceae.
2. Quinidine Gluconate (C26H36N2O9) (Synonyms Quinaglute; Duraquin; Gluconic acid quinidine salt): It is obtained as crystals having mp 175-176.5°C; and soluble in 9 parts of water and 60 parts of ethanol.
3. Quinidine Polygalacturonate (C20H24N2O2.C6H10O7.H2O) [Synonyms Galactoquin; Cardioquin; Naticardina): It is obtained as an amorphous powder mp 180°C (decomposes). The anhydrous substance is found to be insoluble in methanol, ethanol, chloroform, ether, acetone, dioxane; and soluble in 40% methanol or ethanol: 12%; in water at 25°C: ~ 2%.
4. Quindine Hemipentahydrate: It is obtained as prisms from dilute ethanol, mp ~ 168°C, and loses 1/2 H2O on exposure to air.
5. Quinidine Hydrogen Sulphate Tetrahydrate (C20H24N2O2.H2SO4.4H2O) (Synonyms Kiditard; Kinichron; Kinidin Durules; Quiniduran; Chinidin - Duriles; Quinidine Bisulphate): It is obtained as rods which is soluble in 8 parts of water and emitting a distinct blue fluorescence.
6. Neutral Hydroiodide of Quinidine (C20H24N2O2.HI): It is obtained as a crystalline powder when KI is added to a neutral aqueous solution of a quinidine salt. It is very sparingly soluble in water (1 part in 1250 parts at 15°C). It is found to be much less soluble than that of the other cinchona alkaloids.
Quinidine also gives a specific colour test as given below:
Ferrocyanide Test for Quinidine A small quantum (10-15 mg) of a quinidine salt is mixed thoroughly with 0.5-1.0 ml of freshly prepared bromine water in an evaporating dish. The contents are transferred carefully into a test tube with the help of 1 ml of distilled water. To this is added 1 ml of chloroform, contents shaken and then allowed to stay for a few minutes. A few drops of a 10% (w/v) solution of potassium ferrocyanide [K4 Fe(CN)6] and 3 ml of a 5N. NaOH solution are added with continuous shaking. The chloroform layer attains a red colour.
Note: Quinine or its salt under identical treatment gives a negative test, and hence it may be used to distinguish between quinidine and quinine.
Uses
1. It is used as an antiarrhythmic agent (Class 1A)*.
2. It finds its applications as an antimalarial drug.
3. It is most commonly employed to treat various cardiac arrhythmias, namely: atrial flutter, AV junctional and ventricular contractions, atrial and ventricular tachycardia, atrial fibrillation, and premature atrial condition.
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* Class 1A Antiarrhythmic Agent When the antiarrhythmic mechanisms is accomplished through membrane
stabilization.
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