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QUININE SULFATE TABLETS

Category Antiprotozoal (antimalarial).

      Quinine Sulfate Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the labelled amount of (C20H24N2O2)2.H2SO4.2H2O.

Strengths available 260, 300 and 325 mg.

Dose Adults: 600 to 650 mg every 8 hours for 7 days.

      Children: 25 mg per kg of body weight daily in divided doses every 8 hours for 7 days. Contra-indication; Warning; Precaution See under Quinine Sulfate, p. 146.

Contra-indication; Warning; Precaution See under Quinine Sulfate, p. 146.

Additional information

      1. In the treatment of chloroquine-resistant Plasmodium falciparum malaria, quinine is given concurrently with tetracycline or clindamycin.

      2. The medication should be taken with or after meals to minimize gastro-intestinal irritation.

Packaging and storage Quinine Sulfate shall be protected from light.

Identification

      A. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel G as the coating substance and a mixture of 8 volumes of toluene, 2 volumes of acetone and 1 volume of diethylamine as the mobile phase. Apply separately to the plate, 2 μl of each of the following solutions. For solution (A), extract a portion of the powdered tablets, containing 100 mg of quinine sulfate, with 10 ml of a mixture of 2 volumes of chloroform and 1 volume of ethanol and filter. Solution (B) contains 10 mg per ml of Quinine Sulfate RS in the same solvent mixture. After removal of the plate, allow it to dry in air and spray with 0.05 M ethanolic sulfuric acid and then with dilute potassium iodobismuthate TS: the principal spot in the chromatogram obtained from solution (A) corresponds to that obtained from solution (B).

      B. Extract a portion of the powdered tablets, containing 100 mg of quinine sulfate, with 20 ml of water and filter. To 5 ml add 3 drops of bromine TS and then 1 ml of ammonia TS: a green colour is produced.

      C. The filtrate obtained in test B yields reaction A characteristic of sulfates (Appendix 5.1).

Chromatographic purity Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel G as the coating substance.

      Standard preparation, Diluted standard preparation, Related substances preparation, Mobile phase and Procedure Proceed as directed in the Chromato graphic purity under Quinine Sulfate, p. 147.

      Test solution Shake a quantity of the powdered Tablets, equivalent to about 150 mg of quinine sulfate, with 25 ml of ethanol (50 per cent) for 10 minutes, and filter.

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).

      Dissolution medium: 0.01 M hydrochloric acid; 900 ml.

      Apparatus 1: 100 rpm.

      Time: 45 minutes.

      Procedure Determine the amount of (C20H24N2O2)2.H2SO4.2H2O dissolved from absorbances at the maximum at about 248 nm of filtered portions of the test solution, suitably diluted with 0.01 M hydrochloric acid, in comparison with a standard solution having a known concentration of Quinine Sulfate RS in the same medium (Appendix 2.2).

      Tolerances Not less than 75 per cent (Q) of the labelled amount of (C20H24N2O2)2.H2SO4.2H2O is dissolved in 45 minutes.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Methanesulfonic acid solution Add 35.0 ml of methanesulfonic acid to 20.0 ml of glacial acetic acid, dilute with water to 500 ml, and mix.

      Diethylamine solution Dissolve 10.0 ml of diethylamine in water to obtain 100 ml of solution.

      Mobile phase Prepare a mixture of 86 volumes of water, 10 volumes of acetonitrile, 2 volumes of Methanesulfonic acid solution, and 2 volumes of Diethylamine solution. Adjust with Diethylamine solution to a pH of 2.6 if found to be lower.

      System suitability preparation Transfer about 10 mg each of quinine sulfate and dihydroquinine to a 50-ml volumetric flask. Dissolve in 5.0 ml of methanol, dilute with Mobile phase to volume, and mix.

      Assay preparation Weigh and finely powder not less than 20 Quinine Sulfate Tablets. Transfer an accurately weighed portion of the powder, containing about 160 mg of quinine sulfate, to a 100-ml volumetric flask, add 80 ml of methanol, and shake the flask by mechanical means for 30 minutes. Dilute with methanol to volume, and filter, discarding the first 10 ml of the filtrate. Transfer 3.0 ml of the filtrate to a 25-ml volumetric flask, dilute with Mobile phase to volume and mix.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 3.9 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (3 to 10 μm), (b) Mobile phase at a flow rate of about 1 ml per minute, and (c) an ultraviolet photometer set at 235 nm.

      To determine the suitability of the chromatographic system, chromatograph System suitability preparation, and record the peak responses as directed under Procedure: the relative retention times for quinine and dihydroquinine are about 0.67 and 1.0, respectively. The resolution between the quinine and dihydroquinine peaks is not less than 1.2. The relative standard deviation for the peak response of quinine is not more than 2.0 per cent.

      Procedure Separately inject equal volumes (5 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.

      Calculation Calculate the content of (C20H24N2O2)2.H2SO4.2H2O of the sum of quinine sulfate and dihydroquinine sulfate in the portion of the Tablets taken by the expression: 

(2500/3) C(rbU + rdU)/(rbS + rdS),

in which C is the concentration, in mg per ml, of Quinine Sulfate RS in Standard preparation, rbU and rbS are the peak area responses of quinine obtained from Assay preparation and Standard preparation, respectively, and rdU and rdS are the peak area responses of dihydroquinine obtained from Assay preparation and Standard preparation, respectively.

Other requirements Comply with the requirements described under “Tablets” (Appendix 1.16).

 

 

MONOGRAPHS • QUININE SULFATE TABLETS
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หมายเหตุ / Note : TP II 2011 PAGE 148 - 149