Methylprednisolone Sodium Succinate for Injection

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 Sodium Succinate for Injection is a sterile mixture of Methylprednisolone Sodium Succinate with suitable buffers. It may be

prepared from Methylprednisolone Sodium Succinate or from Methylprednisolone Hemisuccinate with the aid of Sodium Hydroxide,

▲Sodium Bicarbonate,▲ (RB 5-May-2022) or Sodium Carbonate. It contains the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount

of methylprednisolone (C₂₂H₃₀O₅) in the volume of constituted solution designated on the label.

2 IDENTIFICATION

A. Infrared Absorption

Sample: Nominally 100 mg of methylprednisolone sodium succinate from Methylprednisolone Sodium Succinate for Injection

Analysis: Transfer the Sample to a separator, dissolve in 10 mL of water, add 1 mL of 3 N hydrochloric acid, and extract immediately with 50

mL of chloroform. Filter the chloroform extract through cotton, evaporate on a steam bath to dryness, and dry under vacuum at 60° for 3 h.

Acceptance criteria: The IR absorption spectrum of a Mineral oil dispersion of the residue so obtained exhibits maxima only at the same

wavelengths as those of a similar preparation of USP Methylprednisolone Hemisuccinate RS.

3 ASSAY

Procedure

Diluent: 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)

Standard stock solution: 0.30 mg/mL of USP Methylprednisolone RS in Diluent

Internal standard solution: 3 mg/mL of USP Fluorometholone RS in tetrahydrofuran

Standard solution: 0.65 mg/mL of USP Methylprednisolone Hemisuccinate RS prepared as follows. Transfer an appropriate amount of USP

Methylprednisolone Hemisuccinate RS to a suitable volumetric flask. Pipet 10% of the flask volume of the Internal standard solution and

10% of the flask volume of the Standard stock solution. Dilute with Diluent to volume.

Sample solution: Transfer a suitable quantity of constituted solutions (mix the constituted solutions prepared from the contents of 10 vials of

Methylprednisolone Sodium Succinate for Injection) equivalent to 50 mg of methylprednisolone to a suitable flask containing 10.0 mL of

the Internal standard solution, and dilute with Diluent to 100.0 mL. Shake thoroughly for 5 min, then allow the phases to separate, discarding

the upper phase.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; packing L3

Flow rate: 1 mL/min

Injection volume: 6 µL

[Note—The order of elution of peaks in the Standard solution is as follows. Internal standard peak, methylprednisolone hemisuccinate peak, and

successive smaller peaks of free methylprednisolone and methylprednisolone 17-hemisuccinate.]

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of methylprednisolone (C₂₂H₃₀O₅) in the portion of constituted Methylprednisolone

Sodium Succinate for Injection taken:

Result = (R₁ / R₂) × (C₁ / C₂) × (M₁ / M₂) × 100

R₁ = ratio of the sum of the peak areas for methylprednisolone hemisuccinate and methylprednisolone 17-hemisuccinate to the

peak area of the internal standard from the Sample solution

R₂ = ratio of the sum of the peak areas for methylprednisolone hemisuccinate and methylprednisolone 17-hemisuccinate to the

peak area of the internal standard from the Standard solution

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

C₂ = nominal concentration of methylprednisolone in the Sample solution (mg/mL)

M₁ = molecular weight of methylprednisolone, 374.47

M₂ = molecular weight of methylprednisolone hemisuccinate, 474.54

To this calculated amount, add the percentage of free methylprednisolone found in the test for Free Methylprednisolone.

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Free Methylprednisolone

Analysis

Samples: Standard solution and Sample solution

Using the chromatograms obtained in the Assay, measure the areas of the peaks from the internal standard and free methylprednisolone.

Calculate the percentage of free methylprednisolone in the portion of Sample solution taken:

Result = (R₁ / R₂) × (C₁ / C₂) × 100

R₁ = peak area ratio of the free methylprednisolone to the internal standard from the Sample solution

R₂ = peak area ratio of the free methylprednisolone to the internal standard from the Standard solution

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

C₂ = nominal concentration of methylprednisolone in the Sample solution (mg/mL)

Acceptance criteria: The amount of free methylprednisolone is NMT 6.6% of the labeled amount of methylprednisolone (C₂₂H₃₀O₅).

5 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

6 SPECIFIC TESTS

pH 〈791〉

Sample solution: 50 mg/mL of methylprednisolone sodium succinate

Acceptance criteria: 7.0–8.0

Sterility Tests 〈71〉: Meets the requirements

Bacterial Endotoxins Test 〈85〉: NMT 0.17 USP Endotoxin Units/mg of methylprednisolone

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 2.0%

Constituted Solution: At the time of use, it meets the requirements for Injections and Implanted Drug Products 〈1〉, Specific Tests, Completeness

and Clarity of Solutions.

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

Other Requirements: Meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for Constitution.

USP Reference Standards 〈11〉

USP Fluorometholone RS

USP Methylprednisolone RS

USP Methylprednisolone Hemisuccinate RS