Hydrocortisone Sodium Succinate for Injection
»Hydrocortisone Sodium Succinate for Injection is a sterile mixture of Hydrocortisone Sodium Succinate and suitable buffers.It may be prepared from Hydrocortisone Sodium Succinate,or from Hydrocortisone 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 hydrocortisone (C21H30O5)in single-compartment containers,or in the volume of solution designated on the label of containers that are constructed to hold in separate compartments the Hydrocortisone Sodium Succinate for Injection and a solvent.
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ.
Labeling— Label it to indicate that the constituted solution prepared from Hydrocortisone Sodium Succinate for Injection is suitable for use only if it is clear,and that the solution is to be discarded after 3days.Label it to indicate that it was prepared by freeze-drying,having been filled into its container in the form of a true solution.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification— It meets the requirements for Identificationtest Aunder Hydrocortisone Sodium Succinate.
Bacterial endotoxins á85ñ— It contains not more than 1.25USP Endotoxin Units per mg of hydrocortisone.
pHá791ñ: between 7.0and 8.0,in a solution containing the equivalent of 50mg of hydrocortisone 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 hydrocortisone— Using the chromatograms obtained in the Assay,measure the areas of the peaks from the internal standard and free hydrocortisone.Calculate the ratio of the area of the free hydrocortisone 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 hydrocortisone in the Assay preparationtaken by the formula:
(100C)(SU/SS),
in which Cis the concentration,in mg per mL,of USP Hydrocortisone RSin the Standard preparation,and SUand SSare the ratios as defined above.The amount of free hydrocortisone is not more than 6.7%of the labeled amount of hydrocortisone.
Other requirements— It meets the requirements for Sterility Tests á71ñ,Uniformity of Dosage Units á905ñ,and Labelingunder Injections á1ñ.
Assay—
Internal standard solution and Mobile solvent—Prepare as directed in the Assayunder Hydrocortisone Hemisuccinate.
Standard preparation— Weigh accurately about 32.5mg of USP Hydrocortisone 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 Hydrocortisone 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 Hydrocortisone Sodium Succinate for Injection.Transfer an accurately measured volume of the resulting constituted solution,equivalent to about 50mg of hydrocortisone,to a suitable flask containing 10.0mLof Internal standard solutionand 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.
Procedure— Proceed as directed for Procedurein the Assayunder Hydrocortisone Hemisuccinate.The order of elution of peaks is that from the internal standard,hydrocortisone hemisuccinate,and successive smaller peaks representing free hydrocortisone and hydrocortisone 17-hemisuccinate,whose relative retention times are about 1.0,1.5,2.0,and 2.5,respectively.Measure the areas of the peaks from the internal standard,hydrocortisone hemisuccinate,and hydrocortisone 17-hemisuccinate.Calculate the ratio of the summation of the areas of the hydrocortisone hemisuccinate and hydrocortisone 17-hemisuccinate peaks to that of the internal standard in the chromatogram obtained from the Standard preparation,RS,and the same ratio in the chromatogram obtained from the Assay preparation,RU.Calculate the quantity,in mg,of hydrocortisone (C21H30O5)in the portion of constituted solution taken by the formula:
0.784(100C)(RU/RS),
in which 0.784is the ratio of the molecular weight of hydrocortisone to that of hydrocortisone hemisuccinate;Cis the concentration,in mg per mL,of USP Hydrocortisone Hemisuccinate RSin the Standard preparation;and RUand RSare the ratios as defined above,and to this quantity add the amount,in mg,of free hydrocortisone found in the test for Free hydrocortisone.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 969
Phone Number:1-301-816-8139