Polythiazide Tablets

General Notices

Action and use

Thiazide diuretic.

Definition

Polythiazide Tablets contain Polythiazide.

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

Content of polythiazide, C11H13ClF3N3O4S3

92.5 to 107.5% of the stated amount.

Identification

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Use the supernatant liquid obtained by extracting a quantity of the powdered tablets containing 4 mg of Polythiazide with 20 mL of methanol and centrifuging.
(2) 0.02% w/v of polythiazide BPCRS in methanol.
chromatographic conditions
(a) Use as the coating silica gel GF254.
(b) Use the mobile phase as described below.
(c) Apply 20 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, examine under ultraviolet light (254 nm) and then treat the plate by Method I and examine again.
mobile phase

20 volumes of acetone, 30 volumes of ether and 50 volumes of toluene.

confirmation

The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).

Tests

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Use the supernatant liquid obtained by shaking a quantity of the powdered tablets containing 10 mg of Polythiazide with 2 mL of acetone and centrifuging.
(2) Dilute 1 volume of solution (1) to 50 volumes with acetone.
chromatographic conditions
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 10 µL of solution (1). Apply 2, 4, 6, 8 and 10 µL of solution (2).
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and reveal the spots using Method I.
mobile phase

10 volumes of methanol and 90 volumes of chloroform.

limits

Assess the intensity of any secondary spot in the chromatogram obtained with solution (1) by reference to the spots in the chromatograms obtained with the applications of solution (2). The sum of the intensities so assessed does not exceed 3% of that of the spot in the chromatogram obtained with solution (1) and no such spot is more intense than the spot in the chromatogram obtained with 10 µL of solution (2) (2%). Disregard any brown spot.

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Polythiazide comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake one tablet with 25 mL of 0.1m potassium dihydrogen orthophosphate adjusted to pH 3.5 with orthophosphoric acid (buffer solution) for 10 minutes, add 25 mL of methanol and shake for a further 20 minutes. Centrifuge 5 mL of the resulting solution for 5 minutes at 2000 revolutions per minute and use the supernatant liquid.
(2) Mix a 0.004% w/v solution of polythiazide BPCRS in methanol with an equal volume of buffer solution.
chromatographic conditions
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 268 nm.
(f) Inject 20 µL of each solution.
mobile phase

45 volumes of methanol and 55 volumes of 0.1m potassium dihydrogen orthophosphate adjusted to pH 3.5 with orthophosphoric acid.

determination of content

Calculate the content of C11H13ClF3N3O4S3 in each tablet using the declared content of C11H13ClF3N3O4S3 in polythiazide BPCRS.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 4 mg of Polythiazide with 100 mL of methanol for 20 minutes, filter and mix equal volumes of the filtrate and 0.1m potassium dihydrogen orthophosphate adjusted to pH 3.5 with orthophosphoric acid (buffer solution).
(2) Mix a 0.004% w/v solution of polythiazide BPCRS in methanol with an equal volume of buffer solution.
chromatographic conditions

The chromatographic conditions described under Uniformity of content may be used.

mobile phase

45 volumes of methanol and 55 volumes of 0.1m potassium dihydrogen orthophosphate adjusted to pH 3.5 with orthophosphoric acid.

determination of content

Calculate the content of C11H13ClF3N3O4S3 in the tablets using the declared content of C11H13ClF3N3O4S3 in polythiazide BPCRS.

Storage

Polythiazide Tablets should be protected from light.