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 volume of Oral Solution, equivalent to about 250 mg of valproic acid, in a separator. Add 40 mL of water and 2 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.

(Official January 1, 2007)

Internal standard solution, Standard preparation, and Chromatographic system— Prepare as directed in the Assay under Valproic Acid Capsules.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 250 mg of valproic acid, to a separator. Add 40 mL of water and 2 mL of hydrochloric acid, mix, and extract gently with 80 mL of n-heptane until the aqueous layer is clear (about 3 minutes). Filter the n-heptane layer through glass wool, collecting the filtrate in a 100-mL volumetric flask. Rinse the separator and the glass wool with small portions of n-heptane, add the rinsings to the 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.

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 each mL of the Oral Solution taken by the formula: in which C is the concentration, in mg per mL, of USP Valproic Acid RS in the Standard preparation; V is the volume, in mL, of Oral Solution taken; and R U and R S are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.