Methylprednisolone Sodium Succinate for Injection

» 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 or Sodium Carbonate. It contains the equivalent of not less than 90.0 percent and not more than 110.0 percent of the labeled amount of methylprednisolone (C22H30O5) in the volume of constituted solution designated on the label.

Packaging and storage— Preserve in Containers for Sterile Solids as described under Injections

USP Reference standards

—

USP Endotoxin RS

USP Fluorometholone RS

USP Methylprednisolone RS

USP Methylprednisolone Hemisuccinate RS

Constituted solution— At the time of use, it meets the requirements for Constituted Solutions under Injections

Identification— It meets the requirements of Identification test A under Methylprednisolone Sodium Succinate.

Bacterial endotoxins

— It contains not more than 0.17 USP Endotoxin Unit per mg of methylprednisolone.

791

: between 7.0 and 8.0, in a solution containing about 50 mg of methylprednisolone sodium succinate per mL.

Loss on drying

731

— Dry it at 105

for 3 hours: it loses not more than 2.0% of its weight.

Particulate matter

788

: meets the requirements for small-volume injections.

Free methylprednisolone— Using the chromatograms obtained in the Assay, measure the areas of the peaks from the internal standard and free methylprednisolone. Calculate the ratio of the area of the free methylprednisolone peak to that of the internal standard in the chromatogram obtained from the Standard preparation, SS, and the same ratio in the chromatogram obtained from the Assay preparation, SU. Calculate the quantity, in mg, of free methylprednisolone in the Assay preparation taken by the formula:

100C(SU / SS)

in which C is the concentration, in mg per mL, of USP Methylprednisolone RS in the Standard preparation; and SU and SS are the ratios as defined above. The amount of free methylprednisolone is not more than 6.6% of the labeled amount of methylprednisolone.

Other requirements— It meets the requirements for Sterility Tests

, Uniformity of Dosage Units

905

, and Labeling under Injections

Assay—

Internal standard solution— Prepare a solution of USP Fluorometholone RS in tetrahydrofuran containing about 3 mg per mL.

Mobile phase— Prepare a filtered mixture of butyl chloride, water-saturated butyl chloride, tetrahydrofuran, methanol, and glacial acetic acid (95:95:14:7:6). Make adjustments if necessary (see System Suitability under Chromatography

621

Standard preparation— Weigh accurately about 32.5 mg of USP Methylprednisolone Hemisuccinate RS, and transfer it to a 50-mL volumetric flask. Add by pipet 5.0 mL of Internal standard solution and 5.0 mL of a solution of glacial acetic acid in chloroform (3 in 100) containing in each mL an accurately known quantity of about 0.30 mg of USP Methylprednisolone RS. Dilute with glacial acetic acid in chloroform (3 in 100) to volume, and mix.

Assay preparation— Mix the constituted solutions prepared from the contents of 10 vials of Methylprednisolone Sodium Succinate for Injection. Transfer an accurately measured volume of the resulting constituted solution, equivalent to about 50 mg of methylprednisolone, to a suitable flask containing 10.0 mL of Internal standard solution, and dilute with glacial acetic acid in chloroform (3 in 100) to 100.0 mL. Shake thoroughly for 5 minutes, then allow the phases to separate, discarding the upper phase.

Chromatographic system (see Chromatography

621

)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L3. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the order of elution of peaks is the internal standard peak, methylprednisolone hemisuccinate peak, and successive smaller peaks of free methylprednisolone and methylprednisolone 17-hemisuccinate.

Procedure— Separately inject equal volumes (about 6 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak areas for the internal standard, methylprednisolone hemisuccinate, and methylprednisolone 17-hemisuccinate. Calculate the quantity, in mg, of methylprednisolone (C22H30O5) in the portion of constituted solution taken by the formula:

0.789(100C)(RU / RS)

in which 0.789 is the ratio of the molecular weight of methylprednisolone to that of methylprednisolone hemisuccinate; C is the concentration, in mg per mL, of USP Methylprednisolone Hemisuccinate RS in the Standard preparation; and RU and RS are the ratios of the sum of the peak areas for methylprednisolone hemisuccinate and methylprednisolone 17-hemisuccinate to the peak area of the internal standard obtained from the Standard preparation and the Assay preparation, respectively. To this quantity add the amount, in mg, of free methylprednisolone found in the test for Free methylprednisolone.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Mary S. Waddell Scientific Liaison 1-301-816-8124	(SM42010) Monographs - Small Molecules 4
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
85	Radhakrishna S Tirumalai, Ph.D. Principal Scientific Liaison 1-301-816-8339	(GCM2010) General Chapters - Microbiology

USP35–NF30 Page 3889