Quinidine Sulfate Tablets

General Notices

Quinidine Sulphate Tablets

Action and use

Class I antiarrhythmic.

Definition

Quinidine Sulfate Tablets contain Quinidine Sulfate.

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

Content of quinidine 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) extract a quantity of the powdered tablets containing 0.1 g of Quinidine 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 quinidine 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. Shake a quantity of the powdered tablets containing 0.25 g of Quinidine 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, wash the residue with 10 mL of ether and dry the residue at 60° at a pressure not exceeding 15 Pa for 2 hours. The pH of a 1% w/v solution of the residue is 6.0 to 6.8, Appendix V L.

C. Extract a quantity of the powdered tablets containing 0.1 g of Quinidine Sulfate with 20 mL of water and filter. The filtrate yields the reactions characteristic of sulfates, Appendix VI.

Other cinchona alkaloids

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) mix a quantity of the powdered tablets containing 50 mg of Quinidine 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 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) but using quinidine sulfate BPCRS in place of quinine sulfate BPCRS. Solution (4) is a mixture of equal volumes of solutions (2) and (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 separately 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 chromatograms 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 allow the chromatography to proceed 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 dihydroquinidine is not greater than 15%, the content of any related substance eluting before quinidine 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. Dissolve as completely as possible using heat a quantity of the powdered tablets containing 0.4 g of Quinidine Sulfate in 40 mL of acetic anhydride and 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

Quinidine Sulfate Tablets should be protected from light.