Co-triamterzide Tablets

General Notices

Triamterene and Hydrochlorothiazide Tablets

Action and use

Potassium-sparing diuretic + thiazide diuretic.

Definition

Co-triamterzide Tablets contain Triamterene and Hydrochlorothiazide in the proportions, by weight, 2 parts to 1 part.

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

Content of triamterene, C12H11N7

95.0 to 105.0% of the stated amount.

Content of hydrochlorothiazide, C7H8ClN3O4S2

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 50 mg of hydrochlorothiazide with 25 mL of acetone, filter, evaporate the filtrate to dryness and dry the residue at 100° for 1 hour. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of hydrochlorothiazide (RS 178).
B. In test A for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (3).
C. In the Assay, the two principal peaks in the chromatogram obtained with solution (3) have the same retention times as the peak due to triamterene in the chromatogram obtained with solution (1) and as the peak due to hydrochlorothiazide in the chromatogram obtained with solution (2).

TESTS

5-Nitroso-2,4,6-triaminopyrimidine

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel HF254 as the coating substance. Apply separately to the plate, as 1.5-cm bands, two 10-µL applications of each of the following four freshly prepared solutions. For solution (1) shake a quantity of the powdered tablets containing 0.10 g of triamterene with 10 mL of anhydrous formic acid for 5 minutes, centrifuge and use the clear supernatant liquid. For solution (2) dissolve 5 mg of 5-nitroso-2,4,6-triaminopyrimidine EPCRS in 50 mL of anhydrous formic acid and dilute 1 volume of the solution to 10 volumes with the same solvent. Prepare solution (3) in the same manner as solution (1) but shaking with 10 mL of solution (2) in place of the formic acid. For solution (4) dissolve 5 mg of hydrochlorothiazide BPCRS in 1 mL of acetone.

Develop over a path of 5 cm using ether as the mobile phase, remove the plate, allow it to dry in air and develop over a path of 10 cm using a 0.05% w/v solution of fluorescein sodium in a mixture of 10 volumes of glacial acetic acid, 10 volumes of methanol and 80 volumes of ethyl acetate as the mobile phase. After removal of the plate, dry it in a current of air, expose to ammonia vapour for a few seconds and examine under ultraviolet light (254 and 365 nm). Any band corresponding to 5-nitroso-2,4,6-triaminopyrimidine in the chromatogram obtained with solution (1) is not more intense than the band in the chromatogram obtained with solution (2) (0.1%). The test is not valid unless, in the chromatogram obtained with solution (3), a band corresponding to the band due to hydrochlorothiazide (obtained with solution (4)), appears above, and is clearly separated from, the band due to 5-nitroso-2,4,6-triaminopyrimidine.

Related substances

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 18m ammonia, 10 volumes of methanol and 90 volumes of ethyl acetate as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.10 g of triamterene with 20 mL of dimethyl sulfoxide, centrifuge and dilute 2 volumes of the supernatant liquid to 50 volumes with methanol. For solution (2) dilute 1 volume of solution (1) to 200 volumes with methanol. For solution (3) dissolve 20 mg of triamterene BPCRS in 4 mL of dimethyl sulfoxide and add sufficient methanol to produce 100 mL. After removal of the plate, allow it to dry in air until the solvent has evaporated and examine under ultraviolet light (365 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%, with reference to the content of triamterene).
B. Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 15 volumes of propan-2-ol and 85 volumes of ethyl acetate as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) vigorously shake a quantity of the powdered tablets containing 50 mg of hydrochlorothiazide with 50 mL of acetone, filter, evaporate the filtrate to dryness and dissolve the residue in 10 mL of acetone. For solution (2) dilute 1 volume of solution (1) to 100 volumes with acetone. After removal of the plate, dry it in a current of air and reveal the spots by Method I. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (1%, with reference to the content of hydrochlorothiazide). Disregard any spot close to the line of application.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 25 mL of acetonitrile and 4 mL of glacial acetic acid to a quantity of the powdered tablets containing 25 mg of hydrochlorothiazide, mix, immediately add 20 mL of water, shake for 15 minutes, dilute to 100 mL with water and filter through glass-fibre paper (Whatman GF/A is suitable). Dilute 10 mL of the filtrate to 100 mL with water. For solution (2) dissolve 50 mg of triamterene BPCRS in 25 mL of acetonitrile, add 4 mL of glacial acetic acid and immediately add sufficient water to produce 100 mL. Dilute 10 mL to 100 mL with water. For solution (3) dissolve 25 mg of hydrochlorothiazide BPCRS in 25 mL of acetonitrile, add 4 mL of glacial acetic acid and immediately add sufficient water to produce 100 mL. Dilute 10 mL to 100 mL with water.

The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak C18 is suitable), (b) a mixture of 2 volumes of methanol, 18 volumes of acetonitrile, 40 volumes of a 0.5% w/v solution of ammonium chloride and 40 volumes of 0.01m sodium perchlorate as the mobile phase with a flow rate of 2.0 mL per minute and (c) a detection wavelength of 273 nm.

Calculate the content of C12H11N7 and C7H8ClN3O4S2 using the declared contents of C12H11N7 and C7H8ClN3O4S2 in triamterene BPCRS and hydrochlorothiazide BPCRS respectively.

Storage

Co-triamterzide Tablets should be protected from moisture.