Quinine Sulfate Tablets

General Notices

Quinine Sulphate Tablets

Action and use

Antiprotozoal (malaria).

Definition

Quinine Sulfate Tablets contain Quinine Sulfate. They are coated.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of quinine sulfate, (C20H24N2O2)2,H2SO4,2H2O

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 10 volumes of diethylamine, 20 volumes of acetone and 80 volumes of toluene as the mobile phase. Apply separately to the plate 2 µL of each of the following solutions. For solution (1) remove any coating from the tablets and extract a quantity of the powdered tablet cores containing 0.1 g of Quinine Sulfate with 10 mL of a mixture of 2 volumes of chloroform and 1 volume of ethanol (96%) and filter. Solution (2) contains 1.0% w/v of quinine sulfate BPCRS in a mixture of 2 volumes of chloroform and 1 volume of ethanol (96%). Solution (3) contains 1.0% w/v each of quinidine sulfate BPCRS and quinine sulfate BPCRS. After removal of the plate, allow it to dry in air and spray with 0.05m ethanolic sulfuric acid and then with dilute potassium iodobismuthate solution. The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2). The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
B. Extract a quantity of the powdered tablets containing 0.25 g of Quinine Sulfate with 25 mL of a mixture of 2 volumes of chloroform and 1 volume of ethanol (96%) and filter. Evaporate the filtrate to dryness and wash the residue with 10 mL of ether. Filter and wash the residue with 10 mL of ether. Dry the residue at 60° at a pressure not exceeding 15 Pa for 2 hours. The pH of a 1% w/v suspension of the residue is 5.7 to 6.6, Appendix V L.
C. Extract a quantity of the powdered tablets containing 0.1 g of Quinine Sulfate with 20 mL of water and filter. The filtrate yields the reactions characteristic of sulfates, Appendix VI.

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using as the medium 900 mL of 0.1m hydrochloric acid and rotating the basket at 100 revolutions per minute. Withdraw a sample of 10 mL of the medium. Measure the absorbance of a layer of suitable thickness of the filtered sample, suitably diluted if necessary, at the maximum at 348 nm, Appendix II B. Calculate the total content of quinine sulfate, (C20H24N2O2)2,H2SO4,2H2O, in the medium taking 136 as the value of A(1%, 1 cm) at the maximum at 348 nm.

Other cinchona alkaloids

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) remove any coating from the tablets and mix a quantity of the powdered tablet cores containing 50 mg of Quinine Sulfate with 20 mL of the mobile phase. Heat gently to dissolve the powder as completely as possible, cool, dilute to 25 mL with the mobile phase and filter, discarding the first few mL of the filtrate. For solution (2) dissolve 20 mg of quinine sulfate BPCRS, with gentle heating if necessary, in 5 mL of the mobile phase and dilute to 10 mL with the mobile phase. Prepare solution (3) in the same manner as solution (2) using quinidine sulfate BPCRS in place of quinine sulfate BPCRS. Solution (4) is a mixture of equal volumes of solution (2) and solution (3). For solution (5) dilute 1 volume of solution (2) to 10 volumes with the mobile phase and dilute 1 volume of the resulting solution to 50 volumes with the mobile phase. Solution (6) contains 0.10% w/v of thiourea in the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS 5 µm is suitable), (b) as the mobile phase with a flow rate of 1.5 mL per minute a solution prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 3.0 g of hexylamine in 700 mL of water, adjusting the pH to 2.8 with 1m orthophosphoric acid, adding 60 mL of acetonitrile and diluting to 1000 mL with water and (c) a detection wavelength of 250 nm for recording the chromatogram obtained with solution (6) and 316 nm for the other solutions.

Inject 10 µL of each of solutions (3) and (6). If necessary adjust the concentration of acetonitrile in the mobile phase so that in the chromatogram obtained with solution (3) the capacity factor of the peak due to quinidine is 3.5 to 4.5, V0 being calculated from the peak due to thiourea in the chromatogram obtained with solution (6). Inject 10 µL of each of solutions (2), (3), (4) and (5). The chromatogram obtained with solution (2) shows a principal peak due to quinine and a peak due to dihydroquinine, with a retention time relative to quinine of about 1.4. The chromatogram obtained with solution (3) shows a principal peak due to quinidine and a peak due to dihydroquinidine, with a retention time relative to quinidine of about 1.2. The chromatogram obtained with solution (4) shows four peaks due to quinine, dihydroquinine, quinidine and dihydroquinidine which are identified by comparison of their retention times with those of the corresponding peaks in the chromatogram obtained with solutions (2) and (3).

The test is not valid unless (a) in the chromatogram obtained with solution (4) the resolution factor between the peaks due to quinine and quinidine is at least 1.5 and the resolution factor between the peaks due to dihydroquinidine and quinine is at least 1.0 and (b) the signal-to-noise ratio of the principal peak in the chromatogram obtained with solution (5) is at least 5.

Inject 10 µL of solution (1) and record the chromatogram for 2.5 times the retention time of the principal peak. Calculate the percentage content of related substances by normalisation, disregarding any peaks the areas of which are less than that of the peak in the chromatogram obtained with solution (5) (0.2%). The content of dihydroquinine is not greater than 10%, the content of any related substance eluted before quinine is not greater than 5% and the content of any other related substance is not greater than 2.5%.

Assay

Weigh and powder 20 tablets and dissolve as completely as possible, using heat, a quantity of the powdered tablets containing 0.4 g of Quinine Sulfate in 40 mL of acetic anhydride. Carry out Method I for non-aqueous titration, Appendix VIII A, using crystal violet solution as indicator. Each mL of 0.1m perchloric acid VS is equivalent to 26.10 mg of (C20H24N2O2)2,H2SO4,2H2O.

Storage

Quinine Sulfate Tablets that are not sugar-coated should be protected from light.

300 mg of Quinine Sulfate is approximately equivalent to 248.6 mg of anhydrous quinine.