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 90.0percent and not more than 110.0percent 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 Solidsas described under Injections á1ñ.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification— It meets the requirements of Identificationtest Aunder Methylprednisolone Sodium Succinate.
Bacterial endotoxins á85ñ— It contains not more than 0.17USP Endotoxin Unit per mg of methylprednisolone.
pHá791ñ: between 7.0and 8.0,in a solution containing about 50mg of methylprednisolone sodium succinate per mL.
Loss on drying á731ñ— Dry it at 105for 3hours:it loses not more than 2.0%of its weight.
Particulate matter á788ñ: 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 preparationtaken by the formula:
100C(SU/SS),
in which Cis the concentration,in mg per mL,of USP Methylprednisolone RSin the Standard preparation;and SUand SSare 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 á71ñ,Uniformity of Dosage Units á905ñ,and Labelingunder Injections á1ñ.
Assay—
Internal standard solution— Prepare a solution of USP Fluorometholone RSin tetrahydrofuran containing about 3mg 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 Suitabilityunder Chromatography á621ñ).
Standard preparation— Weigh accurately about 32.5mg of USP Methylprednisolone Hemisuccinate RS,and transfer it to a 50-mLvolumetric flask.Add by pipet 5.0mLof Internal standard solutionand 5.0mLof a solution of glacial acetic acid in chloroform (3in 100)containing in each mLan accurately known quantity of about 0.30mg of USP Methylprednisolone RS.Dilute with glacial acetic acid in chloroform (3in 100)to volume,and mix.
Assay preparation— Mix the constituted solutions prepared from the contents of 10vials of Methylprednisolone Sodium Succinate for Injection.Transfer an accurately measured volume of the resulting constituted solution,equivalent to about 50mg of methylprednisolone,to a suitable flask containing 10.0mLof Internal standard solution,and dilute with glacial acetic acid in chloroform (3in 100)to 100.0mL.Shake thoroughly for 5minutes,then allow the phases to separate,discarding the upper phase.
Chromatographic system (see Chromatography á621ñ)—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 1.0mLper 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 6µL)of the Standard preparationand the Assay preparationinto 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 0.789is the ratio of the molecular weight of methylprednisolone to that of methylprednisolone hemisuccinate;Cis the concentration,in mg per mL,of USP Methylprednisolone Hemisuccinate RSin the Standard preparation;and RUand RSare 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 preparationand the Assay preparation,respectively.To this quantity add the amount,in mg,of free methylprednisolone found in the test for Free methylprednisolone.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1272
Phone Number:1-301-816-8139