Megestrol Acetate

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

Megestrol Acetate contains NLT 97.0% and NMT 103.0% of megestrol acetate (C₂₄H₃₂O₄), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

3 ASSAY

Procedure

Mobile phase: Acetonitrile and water (55:45)

Diluent: Acetonitrile and water (40:60)

Internal standard solution: 0.8 mg/mL of Propylparaben in acetonitrile

Standard stock solution: 1 mg/mL of USP Megestrol Acetate RS in acetonitrile

Standard solution: 80 μg/mL each of USP Megestrol Acetate RS and propylparaben in Diluent from the Standard stock solution and Internal standard solution, respectively

Sample stock solution: 1 mg/mL of Megestrol Acetate in acetonitrile

Sample solution: 80 μg/mL each of Megestrol Acetate and propylparaben in Diluent from the Sample stock solution and Internal standard solution, respectively

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 25 μL

System suitability

Sample: Standard solution

[Note—The relative retention times for propylparaben and megestrol acetate are about 0.4 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 8.0 between propylparaben and megestrol acetate

Relative standard deviation: NMT 2.0% for the peak response ratio of megestrol acetate to propylparaben

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of megestrol acetate (C₂₄H₃₂O₄) in the portion of Megestrol Acetate taken:

Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak response ratio of megestrol acetate to propylparaben from the Sample solution

R_S = peak response ratio of megestrol acetate to propylparaben from the Standard solution

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

C_U = concentration of Megestrol Acetate in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–103.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%, with a platinum dish being used and ignition at 600 ± 25°

5 SPECIFIC TESTS

Completeness of Solution 〈641〉

Sample: 500 mg in 10 mL of acetone

Acceptance criteria: Meets the requirements

Melting Range or Temperature 〈741〉: 213°–220°, but the range between the beginning and the end of melting does not exceed 3°.

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 20 mg/mL in chloroform

Acceptance criteria: +8.8° to +12.0° (t = 20°)

Water Determination, Method I〈921〉: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light.

USP Reference Standards 〈11〉

USP Megestrol Acetate RS