Divalproex Sodium Delayed-Release Tablets 双丙戊酸钠缓释片美国药典USP39

Divalproex Sodium Delayed-Release Tablets

» Divalproex Sodium Delayed-Release Tablets contain an amount of divalproex

sodium equivalent to 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, light-resistant containers, and store at controlled room temperature.

USP Reference standards 〈11〉—

USP Valproic Acid RS

Identification—The 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.

Dissolution 〈711〉—

acid stage—

Medium: 0.08 N hydrochloric acid (prepared by adding 40 mL of hydrochloric acid to 5000 mL of water, adjusting with 2 N hydrochloric acid to a pH of 1.2, and diluting with water to 6000 mL); 900 mL.

Apparatus 2: 50 rpm.

Time: 1 hour.

Procedure—At the end of 1 hour, carefully transfer the Tablet to a dissolution vessel containing the Medium of the Buffer stage. [note—Do not perform an analysis of the Medium in the Acid stage.]

buffer stage—

Medium: pH 7.5 phosphate buffer (prepared by dissolving 40.83 g of monobasic potassium phosphate and 9.84 g of sodium hydroxide in 5000 mL of water,

adjusting with 0.08 N hydrochloric acid to a pH of 7.5, and diluting with water to 6000 mL); 900 mL.

Apparatus 2: 50 rpm.

Time: 1 hour.

Determine the amount of C8H16O2 dissolved in the Buffer stage by employing the following method.

Citrate buffer—Dissolve 0.5 g of citric acid monohydrate and 0.4 g of dibasic sodium phosphate in 1.0 L of water.

Potassium phosphate buffer—Dissolve 6.8 g of monobasic potassium phosphate and 1.7 g of sodium hydroxide in 1.0 L of water. Adjust with phosphoric acid to a pH of 7.4 ± 0.1.

Mobile phase—Prepare a mixture of Citrate buffer, Potassium phosphate buffer, and acetonitrile (35:35:30). Adjust with phosphoric acid to a pH of 3.0 ± 0.1,

and mix. Filter and degas. Make adjustments if necessary (see System Suitability under Chromatography 〈621〉).

Standard solution—Prepare a solution of USP Valproic Acid RS in the Medium used in the Buffer stage, having a known concentration of about 0.12 mg per mL. [note —A volume of acetonitrile not exceeding 10.0% of the total volume may be used to dissolve the USP Valproic Acid RS.]

Test solution—If necessary, dilute a portion of each filtered solution under test with the Medium used in the Buffer stage to obtain a solution having a concentration of about 0.12 mg per mL.

Chromatographic system (see Chromatography 〈621〉)—The liquid chromatograph is equipped with a 210-nm detector and a 3.9-mm × 15-cm column that contains 4-µm packing L11. The flow rate is about 1.2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the column efficiency is not less than 1000 theoretical plates; the tailing factor

is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure—Separately inject equal volumes (about 50 µL) of the Standard

solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of valproic acid (C8H16O2) dissolved by the formula:

900CD(rU / rS)

in which C is the concentration, in mg per mL, of USP Valproic Acid RS in the Standard solution; D is the dilution factor used to prepare the Test solution; and rU and rS are the peak areas of valproic acid obtained from the Test

solution and the Standard solution, respectively.

Tolerances—Not less than 80% (Q) of the labeled amount of C8H16O2 is dissolved in 1 hour in the Buffer stage.

Uniformity of dosage units 〈905〉: meet the requirements.

Assay—

Citrate buffer—Dissolve 2.0 g of citric acid monohydrate and 1.6 g of dibasic sodium phosphate in 4.0 L of water.

Mobile phase—Prepare a mixture of Citrate buffer and acetonitrile (7:3).

Adjust with phosphoric acid to a pH of 3.0 ± 0.1, and mix. Filter and degas.

Make adjustments if necessary (see System Suitability under Chromatography