A: Infrared Absorption 197K.

B: 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.

Test solution: 4 to 10 mg per mL, in methanol.

Adsorbent: 0.20-mm layer of chromatographic silica gel mixture, prewashed with methanol and air-dried.

Test solution— Dissolve an accurately weighed quantity of Topiramate in methanol to obtain a solution containing approximately 40 mg per mL.

Identification solution— Dissolve a weighed quantity of USP Topiramate Related Compound A RS in methanol to obtain a solution containing about 0.2 mg per mL.

Standard solution A— Dissolve an accurately weighed quantity of USP Topiramate RS in methanol to obtain a final solution having a known concentration of about 40 mg per mL of topiramate.

Standard solution B— Quantitatively dilute Standard solution A with methanol to obtain a solution containing 0.08 mg per mL of topiramate.

Standard solution C— Quantitatively dilute Standard solution A with methanol to obtain a solution containing 0.04 mg per mL of topiramate.

Spray reagent— Prepare a 30 mg per mL solution of phenol in a mixture of alcohol and concentrated sulphuric acid (95:5, v/v).

Application volume: 20 µL.

Developing solvent system— Prepare a mixture of 0.5 M sodium chloride, acetonitrile, and methanol (50:35:15).

Procedure— Proceed as directed for Thin-Layer Chromatography under Chromatography 621. After elution, air-dry the plate, spray the plate with the Spray reagent, and let the plate air-dry. Then dry the plate for 10 minutes in an oven at 125. Examine the plate using visible light, and estimate the percentage of all secondary spots observed in the chromatogram of the Test solution by comparing each spot with the principal spot obtained from the chromatograms of the Standard solutions. [note—Appoximate RF values for topiramate and topiramate related compound A are 0.65 and 0.70, respectively. Disregard any spots observed at the origins of the chromatograms. Disregard any spot corresponding to topiramate related compound A because this impurity should be quantified using the test for Related compounds by HPLC. ]: any single spot is not greater in size and intensity than the spot for Standard solution C; not more than 0.1% of any individual impurity is found; and not more than 0.5% of total impurities by TLC is found.

test 1—

test 2—

Diluent— Prepare a mixture of Purified Water and acetonitrile (80:20).

Solution A— Transfer about 4 g of sodium hydroxide to a 1000-mL volumetric flask. Dissolve in and dilute with water (see Reagents in Chemical Resistance under Containers—Glass 660) to volume, filter, and degas.

Solution B— Use filtered and degassed water.

Solution C— Dilute 50 mL of Solution A with water to 100 mL, filter, and degas.

Mobile phase— Use variable mixtures of Solution A, Solution B, and Solution C as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

Sulfamic acid stock solution— Transfer about 60 mg, accurately weighed, of sulfamic acid to a 100-mL volumetric flask. Dissolve in and dilute with Diluent to volume.

Sulfate stock solution— Transfer about 90.7 mg, accurately weighed, of potassium sulfate to a 100-mL volumetric flask. Dissolve in and dilute with Diluent to volume.

Standard solution— Transfer 3.0 mL each of Sulfamic acid stock solution and Sulfate stock solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix.

Test solution— Transfer about 100 mg, accurately weighed, of Topiramate to a 10-mL volumetric flask. Dissolve in and dilute with Diluent to volume.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a conductivity detector, a 4.0-mm × 5-cm guard column that contains packing L46 and a 4.0-mm × 25-cm column that contains packing L46. The flow rate is about 2.0 mL per minute. The chromatograph is programmed as follows. Chromatograph the Standard solution, and record the peak areas as directed for Procedure: the relative retention time is 1.0 for the sulfate peak and about 0.27 for the sulfamate peak; and the relative standard deviation for replicate injections is not more than 2.0% for both the sulfate and sulfamate peaks.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak areas for the sulfate and sulfamate peaks. Calculate the percentage of sulfate in the portion of Topiramate taken by the formula: in which 96.06 and 174.25 are the molecular weights of the sulfate ion and potassium sulfate, respectively; C is the concentration, in mg per mL, of potassium sulfate in the Standard solution; W is the weight, in mg, of Topiramate taken; and ri and rS are the peak areas of the sulfate ion obtained from the Test solution and the Standard solution, respectively: not more than 0.10% of sulfate ion is found. Calculate the percentage of sulfamate in the portion of Topiramate taken by the formula: in which 96.08 and 97.09 are the molecular weights of sulfamate ion and sulfamic acid, respectively; C is the concentration, in mg per mL, of sulfamic acid in the Standard solution; W is the weight, in mg, of Topiramate taken; and ri and rS are the peak areas of the sulfamate ion obtained from the Test solution and the Standard solution, respectively: not more than 0.10% of sulfamate ion is found.

Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and water (1:1). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Topiramate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 2.0 mg per mL.

Assay preparation— Transfer about 50 mg of Topiramate, accurately weighed, to a 25-mL volumetric flask, and dissolve in and dilute with Mobile phase to volume.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a refractive index detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 0.6 mL per minute. The detector and column temperatures are maintained at 50. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 1500 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 20 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 percentage, of C12H21NO8S in the portion of Topiramate taken by the formula: in which CS is the concentration, in mg per mL, of USP Topiramate RS in the Standard preparation; CU is the concentration, in mg per mL, of Topiramate in the Assay preparation; and rU and rS are the peak areas for topiramate obtained from the Assay preparation and the Standard preparation, respectively.