Spironolactone Tablets

General Notices

Action and use

Aldosterone receptor antagonist; potassium-sparing diuretic.

Definition

Spironolactone Tablets contain Spironolactone.

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

Content of spironolactone, C₂₄H₃₂O₄S

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 0.125 g of Spironolactone with two 10 mL quantities of chloroform, filter, evaporate the combined filtrates to dryness and dissolve the residue in 2.5 mL of chloroform. The infrared absorption spectrum of the resulting solution, Appendix II A, is concordant with the reference spectrum of spironolactone (RS 321).

B. Carry out the method for thin-layer chromatography, Appendix III A, using silica gel GF₂₅₄ as the coating substance and a mixture of 1 volume of water, 24 volumes of cyclohexane and 75 volumes of ethyl acetate as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) extract a quantity of the powdered tablets containing 20 mg of Spironolactone with 10 mL of dichloromethane. Solution (2) contains 0.2% w/v of spironolactone BPCRS in dichloromethane. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). The principal spot in the chromatogram obtained with solution (1) is similar in position and size to that in the chromatogram obtained with solution (2).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 1000 mL of 0.1m hydrochloric acid containing 0.1% w/v sodium dodecyl sulfate and rotate the paddle at 75 revolutions per minute. Withdraw a sample of 10 mL of the medium, filter and measure the absorbance of the filtrate, suitably diluted if necessary, at the maximum at 242 nm, Appendix II B. Calculate the total content of C₂₄H₃₂O₄S in the medium taking 445 as the value of A(1%, 1 cm) at the maximum at 242 nm.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) disperse a quantity of the powdered tablets containing 62.5 mg of Spironolactone with 25 mL of chloroform, place in an ultrasonic bath for 5 minutes, shake for 10 to 15 minutes, centrifuge and filter the supernatant liquid through glass fibre paper (Whatman GF/C is suitable). Repeat the procedure on the residue with a further 25 mL of chloroform. Combine the chloroform extracts and evaporate to dryness using a rotary evaporator. Add 2.5 mL of tetrahydrofuran and 22.5 mL of the mobile phase to the residue. For solution (2) dilute 1 mL of solution (1) to 100 mL with the mobile phase. For solution (3) dissolve 25 mg of canrenone EPCRS in 1 mL of tetrahydrofuran and dilute to 10 mL with the mobile phase. For solution (4) dilute 1 mL of solution (3) to 100 mL with the mobile phase. For solution (5) mix 1 mL each of solutions (1) and (3) and dilute to 100 mL with the mobile phase. For solution (6) dilute 0.5 mL of solution (2) to 10 mL with the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (5 µm) (Spherisorb C8 is suitable), (b) a mixture of 8 volumes of acetonitrile, 18 volumes of tetrahydrofuran and 74 volumes of water as the mobile phase with a flow rate of 1.8 mL per minute and (c) detection wavelengths of 254 nm and 283 nm as directed below.

Inject separately 20 µL of each of solutions (1), (2), (5) and (6) and record the chromatograms for twice the retention time of spironolactone using a detection wavelength of 254 nm. In the chromatogram obtained with solution (1), the sum of the areas of any secondary peaks, other than any peak corresponding to canrenone, is not greater than the area of the peak due to spironolactone in the chromatogram obtained with solution (2) (1%). Disregard any peak the area of which is less than that of the principal peak in the chromatogram obtained with solution (6).

Inject 20 µL of each of solutions (1) and (4) and record the chromatograms using a detection wavelength of 283 nm. The test is not valid unless (a) the chromatogram obtained with solution (5) shows two peaks due to canrenone and spironolactone with a resolution factor greater than 1.4 and (b) the principal peak in the chromatogram obtained with solution (6) has a signal-to-noise ratio of at least 6.

In the chromatogram obtained with solution (1) the area of any peak corresponding to canrenone is not greater than that of the peak due to canrenone in the chromatogram obtained with solution (4) (1%). Calculate the percentage content of canrenone found when recording at 283 nm and the percentage content of the other related substances found when recording at 254 nm. The sum is not greater than 1.0%.

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing 25 mg of Spironolactone add 100 mL of methanol and heat just to boiling, with swirling. Cool, add sufficient methanol to produce 250 mL, dilute 10 mL to 100 mL with methanol and measure the absorbance of the resulting solution at the maximum at 238 nm, Appendix II B. Calculate the content of C₂₄H₃₂O₄S taking 470 as the value of A(1%, 1 cm) at the maximum at 238 nm.

Storage

Spironolactone Tablets should be protected from light.