Medroxyprogesterone 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

Medroxyprogesterone Acetate contains NLT 97.0% and NMT 103.0% of medroxyprogesterone acetate (C₂₄H₃₄O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Analytical wavelength: 241 nm

Sample solution: 10 μg/mL in alcohol

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 2.0%.

3 ASSAY

Procedure

Mobile phase: Acetonitrile and water (40:60)

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

Sample solution: 1 mg/mL of Medroxyprogesterone Acetate in acetonitrile

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of medroxyprogesterone acetate (C₂₄H₃₄O₄) in the portion of Medroxyprogesterone Acetate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

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

4 IMPURITIES

Organic Impurities

Mobile phase: Acetonitrile and water (60:40)

System suitability solution: 40 μg/mL each of megestrol acetate and USP Medroxyprogesterone Acetate RS in Mobile phase

Standard solution: 50 μg/mL of USP Medroxyprogesterone Acetate RS in Mobile phase

Sample solution: 2.5 mg/mL of Medroxyprogesterone Acetate in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between megestrol acetate and medroxyprogesterone acetate, System suitability solution

Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Medroxyprogesterone Acetate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response for each impurity from the Sample solution

r_S = peak response of medroxyprogesterone acetate from the Standard solution

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

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

Acceptance criteria

Individual impurity: NMT 1.0%

Total impurities: NMT 1.5%

Limit of Medroxyprogesterone Acetate Related Compound A

Standard solution: 20 mg/mL of USP Medroxyprogesterone Acetate RS and 0.1 mg/mL of USP Medroxyprogesterone Acetate Related

Compound A RS in methylene chloride

Sample solution: 20 mg/mL of Medroxyprogesterone Acetate in methylene chloride

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 μL

Developing solvent system: Hexanes, tert-butyl methyl ether, and tetrahydrofuran (45:45:10)

Spray reagent: 200 mg/mL of p-toluenesulfonic acid in alcohol

Analysis

Samples: Standard solution and Sample solution

Develop the chromatogram until the solvent front has moved about 10 cm. Allow the plate to air-dry, and develop the chromatogram again until the solvent front has moved about 10 cm. Allow the plate to dry at 120° for 10 min. Spray the plate with Spray reagent. Heat the plate for 10 min at 120°, and examine the plate under UV light at 365 nm.

Acceptance criteria: NMT 0.5%; any blue fluorescent spot with an R value higher than that of the principal spot due to medroxyprogesterone acetate of the Sample solution is not more intense than the corresponding blue fluorescent spot of the Standard solution.

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 10 mg/mL in dioxane

Acceptance criteria: +45° to +51°

 Loss on Drying 〈731〉

Analysis: Dry a sample at 105° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at 25°, excursions permitted between 15° and 30°.

USP Reference Standards 〈11〉

USP Medroxyprogesterone Acetate RS

USP Medroxyprogesterone Acetate Related Compound A RS

4,5β-Dihydromedroxyprogesterone acetate.