Methylprednisolone Hemisuccinate

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 Hemisuccinate contains NLT 97.0% and NMT 103.0% of methylprednisolone hemisuccinate (C₂₆H₃₄O₈), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Change to read:

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

Standard solution: 20 µg/mL of USP Methylprednisolone Hemisuccinate RS in alcohol

Sample solution: 20 µg/mL of methylprednisolone hemisuccinate in alcohol

Analytical wavelength: 243 nm

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

3 ASSAY

Procedure

Solution A: Chloroform and glacial acetic acid (97:3)

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

Internal standard solution: 6 mg/mL of USP Fluorometholone RS in tetrahydrofuran

Standard solution: 0.4 mg/mL of USP Methylprednisolone Hemisuccinate RS prepared as follows. Transfer a suitable quantity of USP

Methylprednisolone Hemisuccinate RS to a suitable volumetric flask, and add 5.0% of the flask volume of Internal standard solution. Dilute

with Solution A to volume.

Sample solution: 0.4 mg/mL of Methylprednisolone Hemisuccinate prepared as follows. Transfer a suitable quantity of Methylprednisolone

Hemisuccinate to a suitable volumetric flask, and add 5.0% of the flask volume of Internal standard solution. Dilute with Solution A to

volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 30-cm; packing L3

Injection volume: 4–8 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between methylprednisolone hemisuccinate and fluorometholone

Relative standard deviation: NMT 2.0% for six replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methylprednisolone hemisuccinate (C₂₆H₃₄O₈) in the portion of Methylprednisolone Hemisuccinate taken:

Result = (R₁ / R₂) × (C₁ / C₂) × 100

R₁ = peak area ratio of methylprednisolone hemisuccinate to fluorometholone from the Sample solution

R₂ = peak area ratio of methylprednisolone hemisuccinate to fluorometholone from the Standard solution

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

C₂ = concentration of Methylprednisolone Hemisuccinate 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, formic acid, and water (255:1:745)

Diluent: Tetrahydrofuran, acetonitrile, acetic acid, and water (25:25:3:47)

Standard solution: 0.02 mg/mL of USP Methylprednisolone Hemisuccinate RS in Diluent

Sample solution: 1 mg/mL of Methylprednisolone Hemisuccinate in Diluent. Shake or sonicate to aid in solubilization.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 20-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 5000 theoretical plates

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (r₁ / r₂) × (C₁ / C₂) × 100

r₁ = peak area of each impurity from the Sample solution

r₂ = peak area of methylprednisolone hemisuccinate from the Standard solution

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

C₂ = concentration of Methylprednisolone Hemisuccinate 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 of Methylprednisolone Hemisuccinate in dioxane

Acceptance criteria: +87° to +95°

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 containers.

USP Reference Standards 〈11〉

USP Fluorometholone RS

USP Methylprednisolone Hemisuccinate RS