Co-amilofruse Tablets

Action and use

Potassium sparing diuretic + loop diuretic.

Definition

Co-amilofruse Tablets contain Amiloride Hydrochloride Dihydrate and Furosemide in the proportions one part of anhydrous amiloride hydrochloride to eight parts of Furosemide.

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

Content of anhydrous amiloride hydrochloride, C₆H₈ClN₇O,HCl

95.0 to 105.0% of the stated amount.

Content of furosemide, C₁₂H₁₁ClN₂O₅S

95.0 to 105.0% of the stated amount.

Identification

A. In the test for Related substances, the principal spots in the chromatogram obtained with solution (2) correspond to those in the chromatograms obtained with solutions (4) and (5) respectively.

B. In the Assay, the retention times of the two principal peaks in the chromatogram obtained with solution (1) are the same as those in the chromatogram obtained with solution (4).

TEST

Related substances

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

(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 80 mg of Furosemide with 16 mL of methanol for 5 minutes, centrifuge and use the supernatant liquid.

(2) Dilute 1 volume of solution (1) to 10 volumes with methanol.

(3) Dilute 1 volume of solution (2) to 20 volumes with methanol.

(4) 0.05% w/v of furosemide BPCRS in methanol.

(5) 0.00625% w/v of amiloride hydrochloride BPCRS in methanol.

(6) 0.0025% w/v of 4-chloro-5-sulfamoylanthranilic acid BPCRS in methanol.

(7) 0.00031% w/v of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate BPCRS in methanol

chromatographic conditions

(a) Use as the coating silica gel F₂₅₄.

(b) Use the mobile phase as described below.

(d) Develop the plate to 15 cm.

(e) After removal of the plate, dry it in a current of air and examine under ultraviolet light (254 nm) and examine under ultraviolet light (365 nm).

mobile phase

5 volumes of glacial acetic acid, 5 volumes of methanol and 90 volumes of chloroform.

limits

At 254 nm

In the chromatogram obtained with solution (1) any secondary spot other than any spot remaining on the line of application or any spots corresponding to either of the named impurities is not more intense than the spot in the chromatogram obtained with solution (3) (0.5%, with reference to the content of furosemide)

At 365 nm

In the chromatogram obtained with solution (1) any spot corresponding to methyl 3,5-diamino-6-chloropyrazine-2-carboxylate is not more intense than the spot in the chromatogram obtained with solution (7) (0.5%, with reference to the content of anhydrous amiloride hydrochloride). Reveal the spots by Method I. In the chromatogram obtained with solution (1) any spot corresponding to 4-chloro-5-sulfamoylanthranilic acid is not more intense than the spot in the chromatogram obtained with solution (6) (0.5%, with reference to the content of furosemide).

Assay

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

(1) Disperse a quantity of the powdered tablets containing 40 mg of Furosemide in 70 mL of a mixture of 4 volumes of water and 6 volumes of methanol adjusted to pH 2.0 with orthophosphoric acid, mix with the aid of ultrasound for 20 minutes, dilute to 100 mL with the same solvent mixture, mix, filter and dilute 20 mL of the filtrate to 50 mL with the same solvent mixture.

(2) 0.002% w/v of amiloride hydrochloride BPCRS in a mixture of 4 volumes of water and 6 volumes of methanol adjusted to pH 2.0 with orthophosphoric acid.

(3) 0.016% w/v of furosemide BPCRS in a mixture of 4 volumes of water and 6 volumes of methanol adjusted to pH 2.0 with orthophosphoric acid.

(4) 0.002% w/v of amiloride hydrochloride BPCRS and 0.016% w/v of furosemide BPCRS in a mixture of 4 volumes of water and 6 volumes of methanol adjusted to pH 2.0 with orthophosphoric acid.

chromatographic conditions

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (Spherisorb ODS1 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 361 nm.

(f) Inject 20 µL of each solution.

mobile phase

0.02m solution of sodium hexanesulfonate in a mixture of 4 volumes of water and 6 volumes of methanol, the pH of the solution adjusted to 4.0 with 1m acetic acid.

system suitability

The assay is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks due to furosemide and amiloride is at least 2.5.

determination of content

Calculate the content of C₆H₈ClN₇O,HCl and C₁₂H₁₁ClN₂O₅S using the declared content of C₆H₈ClN₇O,HCl and C₁₂H₁₁ClN₂O₅S in amiloride hydrochloride BPCRS and furosemide BPCRS, respectively.

Storage

Co-amilofruse Tablets should be protected from light.

Labelling

The quantity of Amiloride Hydrochloride Dihydrate is stated in terms of the equivalent amount of anhydrous amiloride hydrochloride.