Spironolactone Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Spironolactone Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of spironolactone (C₂₄H₃₂O₄S).

2 IDENTIFICATION

Change to read:

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-Aug-2021)

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1- Aug-2021)

3 ASSAY

Change to read:

PROCEDURE

Mobile phase: Methanol and water (60:40) Diluent: Acetonitrile and water (50:50)

Standard solution: 0.5 mg/mL of USP Spironolactone RS in Diluent

Sample stock solution: Nominally 1 mg/mL of spironolactone in Diluent prepared as follows. Weigh NLT 10 Tablets, and transfer to a suitable volumetric flask.  (USP 1-Aug-2021) Add a sufficient quantity of Diluent, shake for about 30 min, and sonicate for 30 min or until the Tablets are disintegrated. Cool the solution to room temperature, dilute with Diluent to volume, and centrifuge a suitable portion of the mixture.

Sample solution: Nominally 0.5 mg/mL of spironolactone in Diluent from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 210–400 nm. (USP 1-Aug-2021)

Column: 4.6-mm × 15-cm; 5-µm (USP 1-Aug-2021) packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of spironolactone (USP 1-Aug-2021)

System suitability

Sample: Standard solution Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.5% Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of spironolactone (C₂₄H₃₂O₄S) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of spironolactone (USP 1-Aug-2021) from the Sample solution

r_S = peak response of spironolactone (USP 1-Aug-2021) from the Standard solution

C_S = concentration of USP Spironolactone RS in the Standard solution (mg/mL)

C_U = nominal concentration of spironolactone in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION 〈711〉

Medium: 0.1 N hydrochloric acid containing 0.1% of sodium dodecyl sulfate; 1000 mL Apparatus 2: 75 rpm

Time: 60 min

Standard solution: A known concentration of USP Spironolactone RS in Medium. [NOTE—A volume of alcohol not exceeding 1% of the final volume of the solution may be used to prepare the Standard solution.]

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, as necessary in comparison with the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.) (USP 1-Aug-2021)

Mode: UV

Analytical wavelength: 242 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled (USP 1-Aug-2021) amount of spironolactone (C₂₄H₃₂O₄S) dissolved:

Result = (A_U/A_S) × C_S × D × V × (1/L) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Spironolactone RS in the Standard solution (mg/mL)

D = dilution factor for the Sample solution

V = volume of Medium, 1000 mL

L = label claim of spironolactone (mg/Tablet)

(USP 1-Aug-2021)

Tolerances: NLT 75% (Q ) of the labeled amount of spironolactone (C₂₄H₃₂O₄S) is dissolved.

UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the requirements Add the following:

5 IMPURITIES

ORGANIC IMPURITIES

Diluent: Acetonitrile and water (50:50)

Mobile phase: Acetonitrile, tetrahydrofuran, methanol, and water (15:20:425:540)

Standard stock solution A: 100 µg/mL of USP Spironolactone RS prepared as follows. Dissolve a suitable amount of USP Spironolactone RS in a suitable volumetric flask in about 10% of the total volume with tetrahydrofuran. Dilute with Diluent to volume.

Standard stock solution B: 100 µg/mL of USP Spironolactone Related Compound A RS prepared as follows. Dissolve a suitable amount of USP Spironolactone Related Compound A RS in a suitable volumetric flask in about 10% of the total volume with tetrahy drofuran. Dilute with Diluent to volume.

Sensitivity solution: 2 µg/mL of USP Spironolactone RS in Diluent, from Standard stock solution A

Standard solution: 4 µg/mL each of USP Spironolactone RS and USP Spironolactone Related Compound A RS in Diluent, from Standard stock solution A and Standard stock solution B

Sample solution: Nominally 2 mg/mL of spironolactone in Diluent prepared as follows. Transfer a suitable number of Tablets into a volumetric flask. Add about 10% of the total volume of tetrahydrofuran and swirl to disintegrate. Add NLT 80% of the total volume of Diluent. Shake by mechanical means for 30 min. Follow by sonication for 30 min and then cool to room temperature. Dilute with Diluent to volume. Centrifuge and use the supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L1

Column temperature: 40°

Flow rate: 1.0 mL/min Injection volume: 20 µL

Run time: NLT 2.5 times the retention time of spironolactone

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between spironolactone and spironolactone related compound A, Standard solution

Relative standard deviation: NMT 5.0% for spironolactone and spironolactone related compound A, Standard solution Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of spironolactone related compound A in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of spironolactone related compound A from the Sample solution

r_S = peak response of spironolactone related compound A from the Standard solution

C_S = concentration of USP Spironolactone Related Compound A RS in the Standard solution (mg/mL)

C_U = nominal concentration of spironolactone in the Sample solution (mg/mL)

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of spironolactone from the Standard solution

C_S = concentration of USP Spironolactone RS in the Standard solution (mg/mL)

C_U = nominal concentration of spironolactone in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. The reporting threshold is 0.1%.

Table 1

6 ADDITIONAL REQUIREMENTS

Change to read:

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature. (USP 1-Aug-2021)

Change to read:

USP REFERENCE STANDARDS 〈11〉

USP Spironolactone RS

USP Spironolactone Related Compound A RS

(2’R)-3’,4’-Dihydro-5’H-spiro[androst-4,6-diene-17,2’-furan]-3,5’-dione.

C₂₂H₂₈O₃       340.46 (USP 1-Aug-2021)