Methylprednisolone 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

Methylprednisolone Acetate contains NLT 97.0% and NMT 103.0% of methylprednisolone acetate (C₂₄H₃₂O₆), 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: 243 nm

Standard solution: 10 µg/mL of USP Methylprednisolone Acetate RS in alcohol

Sample solution: 10 µg/mL of methylprednisolone acetate in alcohol

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%.

3 ASSAY

Procedure

Mobile phase: n-Butyl chloride, water-saturated n-butyl chloride, tetrahydrofuran, methanol, and glacial acetic acid (95:95:14:7:6)

Internal standard solution: 6 mg/mL of Prednisone prepared as follows. Transfer an appropriate amount of prednisone to a suitable

volumetric flask. Add 3% of the flask volume of glacial acetic acid, and sonicate. Dilute with chloroform to volume, slowly adding the

chloroform. Sonicate, and shake to dissolve.

Standard solution: 0.2 mg/mL of USP Methylprednisolone Acetate RS prepared as follows. Transfer an appropriate amount of USP

Methylprednisolone Acetate RS to a suitable volumetric flask, and add 5% of the flask volume of the Internal standard solution. Dilute with

chloroform to volume, and shake to dissolve.

Sample solution: 0.2 mg/mL of Methylprednisolone Acetate prepared as follows. Transfer an appropriate amount of methylprednisolone

acetate to a suitable volumetric flask, and add 5% of the flask volume of the Internal standard solution. Dilute with chloroform to volume,

and shake to dissolve.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 25-cm; packing L3

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for methylprednisolone acetate and prednisone are about 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 2.5 between methylprednisolone acetate and prednisone

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methylprednisolone acetate (C₂₄H₃₂O₆) in the portion of Methylprednisolone Acetate taken:

Result = (R₁ / R₂) × (C₁ / C₂) × 100

R₁ = peak height ratio of methylprednisolone acetate to prednisone from the Sample solution

R₂ = peak height ratio of methylprednisolone acetate to prednisone from the Standard solution

C₁ = concentration of USP Methylprednisolone Acetate RS in the Standard solution (mg/mL)

C₂ = concentration of Methylprednisolone Acetate in the Sample solution (mg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

Mobile phase: Tetrahydrofuran and water (51:149)

Diluent: Tetrahydrofuran, acetonitrile, glacial acetic acid, and water (250:250:1:499)

Standard solution: 20 µg/mL of USP Methylprednisolone Acetate RS in Diluent. Sonicate, if necessary, to dissolve.

Sample solution: 1 mg/mL of Methylprednisolone Acetate in Diluent. Sonicate, if necessary, to dissolve.

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

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (r₁ / r₂) × (C₁ / C₂) × 100

r₁ = peak response for each impurity from the Sample solution

r₂ = peak response for methylprednisolone acetate from the Standard solution

C₁ = concentration of USP Methylprednisolone Acetate RS in the Standard solution (mg/mL)

C₂ = concentration of Methylprednisolone Acetate in the Sample solution (mg/mL)

Acceptance criteria

Any individual impurity: NMT 1.0%

Total impurities: NMT 2.0%

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation 〈781S〉

Sample solution: 10 mg/mL in dioxane

Acceptance criteria: +97° to +105°

Loss on Drying 〈731〉

Analysis: Dry 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 Methylprednisolone Acetate RS