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Valproic Acid Capsules
» Valproic Acid Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of valproic acid (C8H16O2).
Packaging and storage— Preserve in tight containers, at controlled room temperature.
A: The retention time ratios of the valproic acid peak to the internal standard peak obtained from the Standard preparation and the Assay preparation as directed in the Assay do not differ by more than 2.0%.
B: Place a portion of Capsule contents, equivalent to about 250 mg of valproic acid, in a separator. Add 20 mL of 1 N sodium hydroxide, shake, and allow the layers to separate. Transfer the aqueous layer to a second separator, add 4 mL of hydrochloric acid, mix, and extract with 40 mL of n-heptane. Filter the n-heptane layer through glass wool into a beaker, and evaporate the solvent completely on a steam bath with the aid of a current of air. Transfer 2 drops of the residue to a test tube containing 0.5 mL each of potassium iodide solution (1 in 50) and potassium iodate solution (1 in 25), and mix: a yellow color is produced.
Disintegration 701: 15 minutes, determined as directed for Soft Gelatin Capsules.
Dissolution 711
Medium: a solution containing 5 mg per mL of sodium lauryl sulfate in simulated intestinal fluid TS (prepared without the enzyme and with monobasic sodium phosphate instead of monobasic potassium phosphate), adjusted with 5 M sodium hydroxide to a pH of 7.5; 900 mL.
Apparatus 2: 50 rpm.
Time: 60 minutes.
Internal standard solution and Chromatographic system—Proceed as directed in the Assay.
Standard preparation— Prepare a solution of USP Valproic Acid RS having a concentration similar to that of the solution under test. Transfer 10.0 mL to a suitable container. Add about 3.0 g of sodium chloride, and mix on a vortex mixer for 5 minutes. Add about 1 mL of 6 N hydrochloric acid and 5.0 mL of Internal standard solution, and shake for 2 minutes. Allow the phases to separate, remove the n-heptane layer, and filter. Discard the aqueous layer.
Test preparation— Transfer 10.0 mL of the solution under test to a suitable container. Proceed as directed for Standard preparation, beginning with “Add about 3.0 g”.
Procedure— Proceed as directed in the Assay.
Tolerances— Not less than 85% (Q) of the labeled amount of C8H16O2 is dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements, chloroform being used as the solvent in the procedure for Soft Capsules.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Internal standard solution— Dissolve a quantity of biphenyl in n-heptane to obtain a solution having a concentration of about 5 mg per mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Valproic Acid RS in n-heptane to obtain a solution having a known concentration of about 2.5 mg per mL. Transfer 5.0 mL to a container equipped with a closure. Add 2.0 mL of Internal standard solution, close the container, and mix.
Assay preparation— Transfer not fewer than 20 Capsules to a blender jar or other container, add about 150 mL of methylene chloride, and cool in a solid carbon dioxide-acetone mixture until the contents have solidified. If necessary, transfer the mixture of Capsules and methylene chloride to a blender jar, and blend with a high-speed blender until all the solids are reduced to fine particles. Transfer the mixture to a 500-mL volumetric flask, add n-heptane to volume, mix, and allow solids to settle. Transfer an accurately measured volume of this solution, equivalent to 250 mg of valproic acid, to a 100-mL volumetric flask, dilute with n-heptane to volume, and mix. Transfer 5.0 mL to a container equipped with a closure. Add 2.0 mL of Internal standard solution, close the container, and mix.
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 150, and the injection port and the detector block temperatures are maintained at about 250. Dry helium is used as the carrier gas at a flow rate of about 40 mL per minute. Chromatograph the Standard preparation, measure the peak responses, and calculate the ratio, R S, as directed for Procedure: the relative retention times are about 0.5 for valproic acid and 1.0 for biphenyl; the resolution, R, between valproic acid and biphenyl is not less than 3.0; the relative standard deviation 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 responses for valproic acid and biphenyl. Calculate the quantity, in mg, of valproic acid (C8H16O2) in the portion of Capsules taken by the formula:
100 C(RU / RS),
in which C is the concentration, in mg per mL, of USP Valproic Acid RS in the Standard preparation; and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 2235
Phone Number : 1-301-816-8330