Valproate Sodium Injection
» Valproate Sodium Injection is a sterile aqueous solution of sodium valproate, formed from the interaction of Valproic Acid and Sodium Hydroxide, in Water for Injection, and one or more suitable buffering or sequestering agents. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of valproic acid (C8H16O2). It contains no antimicrobial agents.
Packaging and storage Preserve in single-dose Containers for Injection as described under Injections 1, preferably of Type I glass. Store at controlled room temperature, excursions allowed between 15 and 30.
Labeling Label it to state the name and quantity of any buffering or sequestering agent used.
USP Reference standards 11
USP Endotoxin RS
A: The relative retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B: It meets the requirements of the tests for Sodium 191.
Bacterial endotoxins 85 It contains not more than 23 USP Endotoxin Units per mL of Injection.
Sterility 71 It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined.
pH 791: between 7.0 and 9.0.
Particulate matter 788 It meets the requirements for small-volume injections.
Other requirements It meets the requirements under Injections 1.
Internal standard solution Dissolve a quantity of biphenyl in methylene chloride to obtain a solution containing 5 mg per mL.
Standard stock preparation Prepare a solution of USP Valproic Acid RS in Internal standard solution having a concentration of about 8 mg per mL.
Standard preparation Transfer 5.0 mL of the Standard stock preparation into a 50-mL volumetric flask, and dilute with methylene chloride to volume.
Assay preparation Transfer an accurately measured volume of Injection, equivalent to 400 mg of valproic acid, into a suitable container; add about 20 mL of 5% (v/v) hydrochloric acid; shake by mechanical means for 2 minutes; add 50.0 mL of the Internal standard solution; and shake by mechanical means for 1 hour. Allow the phase to separate (approximately 1 hour). The bottom organic layer remains cloudy, and at times a slight emulsion may persist. If an emulsion forms, break it up by stirring it with a glass rod. Pipet 5 mL of the extract from the bottom organic layer into a 50-mL volumetric flask, and dilute with methylene chloride.
Chromatographic system (see Chromatography 621) The gas chromatograph is equipped with a flame-ionization detector and a 2-mm × 1.8-m glass column packed with 10% phase G34 on 80- to 100-mesh support S1A. The column temperature is maintained at about 155, the injection port temperature is maintained at about 275, and the detector block temperature is maintained at about 300. Dry helium is used as the carrier gas, at a flow rate of about 20 mL per minute. Chromatograph the Standard preparation as directed for Procedure: the resolution, R, between the valproic acid and biphenyl peaks is not less than 3.0; and the relative standard deviation of the peak area ratios for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 2 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak areas for the valproic acid and biphenyl peaks. Calculate the quantity, in mg, of valproic acid in the volume of Injection taken by the formula:
C(RU / RS) Din which C is the concentration, in mg per mL, of USP Valproic Acid RS in the Standard preparation; RU and RS are the peak area ratios obtained from the Assay preparation and the Standard preparation, respectively; and D is the appropriate dilution factor used to prepare the Assay preparation.
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USP35NF30 Page 4991Pharmacopeial Forum: Volume No. 34(2) Page 312