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.
Identification—
The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 
711
—
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).
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%.
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.
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 621).
621).
Standard preparation—
Prepare a solution of USP Valproic Acid RS in Mobile phase having a known concentration of about 0.5 mg per mL.
Assay preparation—
Transfer a number of whole Tablets containing the equivalent of about 2500 mg of valproic acid into a 250-mL volumetric flask. Add 150 mL of Mobile phase, and sonicate with frequent swirling for 30 minutes or until the Tablets completely disintegrate. Allow the solution to cool down to room temperature, and then dilute with Mobile phase to volume. Transfer 5.0 mL of the resulting solution to a 100-mL volumetric flask. Dilute with Mobile phase to volume, and mix.
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 0.9 mL per minute. Chromatograph the Standard preparation, 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%.
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 0.9 mL per minute. Chromatograph the Standard preparation, 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 15 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of valproic acid (C8H16O2) in the portion of Tablets taken by the formula:
5000C(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 areas of valproic acid obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Ravi Ravichandran, Ph.D.
Senior Scientist 1-301-816-8330 |
(MDPP05) Monograph Development-Psychiatrics and Psychoactives |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientist 1-301-816-8106 |
(BPC05) Biopharmaceutics05 |
USP32–NF27 Page 2188
Pharmacopeial Forum: Volume No. 31(1) Page 153
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.