Methylprednisolone

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 contains NLT 97.0% and NMT 103.0% of methylprednisolone (C₂₂H₃₀O₅), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K ▲or 197A▲ (USP 1-Dec-2023)

Delete the following:

▲B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy:▲ (USP 1-Dec-2023)

Add the following:

▲B. 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-Dec-2023)

Delete the following:

▲C.▲ (USP 1-Dec-2023)

3 ASSAY

Change to read:

Procedure

Solution A: Acetonitrile, tetrahydrofuran, phosphoric acid, and water (10:1.5:0.1:90)

Solution B: Acetonitrile, tetrahydrofuran, and phosphoric acid (100:1.5:0.1)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile, phosphoric acid, and water (50:0.1:50)

System suitability solution: 0.6 mg/mL of USP Methylprednisolone System Suitability Mixture RS in Diluent

Standard solution: 0.6 mg/mL of USP Methylprednisolone RS in Diluent

Sample solution: 0.6 mg/mL of Methylprednisolone in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 247 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: System suitability solution and Standard solution

[Note—The relative retention times for methylprednisolone related compound A and methylprednisolone are 0.93 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.7 between methylprednisolone related compound A and methylprednisolone, System suitability solution

Relative standard deviation: NMT 1.10%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methylprednisolone (C₂₂H₃₀O₅) in the portion of Methylprednisolone taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of methylprednisolone from the Sample solution

rₛ = peak response of methylprednisolone from the Standard solution

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

Cᵤ = concentration of Methylprednisolone in the Sample solution (mg/mL) ▲ (USP 1-Dec-2023)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Change to read:

Organic Impurities

▲Solution A, Solution B, Mobile phase, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.0003 mg/mL of USP Methylprednisolone RS in Diluent

Standard solution: 0.006 mg/mL of USP Methylprednisolone RS in Diluent

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note—See Table 2 for the relative retention times. The relative retention times in Table 2 are provided for information that could aid in peak assignment.]

Table 2

Suitability requirements

Resolution: NLT 1.7 between methylprednisolone and methylprednisolone related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

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

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1 / F) × 100

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of methylprednisolone from the Standard solution

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

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

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

ᵃ Sum of trans isomer and cis isomer.

▲ (USP 1-Dec-2023)

5 SPECIFIC TESTS

Change to read:

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: ▲10 mg/mL in alcohol▲ (USP 1-Dec-2023)

Acceptance criteria: ▲+97.0° to +103.0°, calculated on the dried basis▲ (USP 1-Dec-2023)

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight, light-resistant containers. ▲Store at controlled cold temperature.▲ (USP 1-Dec-2023)

Change to read:

USP Reference Standards 〈11〉

USP Methylprednisolone RS

▲USP Methylprednisolone System Suitability Mixture RS

Contains a mixture of the following 10 compounds:

Methylprednisolone.

Methylprednisolone related compound A:

17,21-Dihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione.

C₂₂H₂₈O₅ 372.46

Methylprednisolone related compound B:

11β,17,21,21-Tetrahydroxy-6α-methylpregna-1,4-diene-3,20-dione.

C₂₂H₃₀O₆ 390.48

Methylprednisolone related compound C:

11β-Hydroxy-6α-methylandrosta-1,4-diene-3,17-dione.

C₂₀H₂₆O₃ 314.43

Methylprednisolone related compound D:

11β,20-Dihydroxy-6α-methylpregna-1,4,17(20)-triene-3,21-dione.

C₂₂H₂₈O₄ 356.46

Methylprednisolone related compound E:

11β-Hydroxy-6α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid.

C₂₀H₂₄O₄ 344.45

Methylprednisolone related compound F:

11β,17,21-Trihydroxy-6α-methylpregn-4-ene-3,20-dione.

C₂₂H₃₂O₅ 376.49

Methylprednisolone related compound G:

17,21-Dihydroxy-6α-methylpregna-1,4,9(11)-triene-3,20-dione.

C₂₂H₂₈O₄ 356.46

Methylprednisolone related compound H:

11β,17,21-Trihydroxy-6β-methylpregna-1,4-diene-3,20-dione.

C₂₂H₃₀O₅ 374.48

Impurity I: Unknown structure.

▲ (USP 1-Dec-2023)