» Ethosuximide Capsules contain not less than 93.0 percent and not more than 107.0 percent of the labeled amount of C7H11NO2, present in the form of a solution of Ethosuximide in Polyethylene Glycol 400 or other suitable solvent.
Packaging and storage Preserve in tight containers.
USP Reference standards 11
Identification Place a portion of the Capsule contents, equivalent to about 300 mg of ethosuximide, in a separator containing 50 mL of ether. Shake with three 10-mL portions of water, discarding the aqueous extracts. Add about 5 g of anhydrous sodium sulfate, swirl for 3 minutes, and filter through a small pledget of cotton that previously has been washed with ether, into a small flask. Evaporate the ether solution at room temperature in a current of air to dryness, and dissolve the residue in 5 mL of chloroform: the IR absorption spectrum of the solution, in the region between 3000 cm1 and 1650 cm1, determined in a 0.1-mm cell, exhibits maxima only at the same wavelengths as that of a 1 in 15 solution of USP Ethosuximide RS in chloroform.
Dissolution, Procedure for a Pooled Sample 711
Medium: pH 6.8 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.
Apparatus 1: 50 rpm.
Time: 30 minutes.
Mobile phase Prepare a degassed and filtered mixture of water and acetonitrile (80:20).
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 4-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation is not more than 2.0%.
Procedure Inject an accurately measured volume (about 50 µL) of a filtered portion of the solution under test into the chromatograph, record the chromatogram, and measure the response for the major peak. Determine the amount of C7H11NO2 dissolved by comparison with a Standard solution, having a known concentration of USP Ethosuximide RS in the same Medium, similarly chromatographed.
Tolerances Not less than 80% (Q) of the labeled amount of C7H11NO2 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Limit of 2-ethyl-2-methylsuccinic acid
Mobile phase, System suitability solution, and Chromatographic system Proceed as directed in the Assay.
Standard solution Dissolve an accurately weighed quantity of 2-ethyl-2-methylsuccinic acid in Mobile phase, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.026 mg per mL.
Test solution Transfer 20 Capsules into a 2-liter volumetric flask, dissolve in 1800 mL of Mobile phase, dilute with Mobile phase to volume, and mix.
Procedure Separately inject equal volumes (about 10 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 percentage of 2-ethyl-2-methylsuccinic acid in the portion of Capsules taken by the formula:
100(CS / CU)(rU / rS)in which CS is the concentration, in mg per mL, of 2-ethyl-2-methylsuccinic acid in the Standard solution; CU is the concentration, in mg per mL, of ethosuximide in the Test solution, based on the number of Capsules taken, the labeled quantity, in mg, of ethosuximide in each Capsule, and the extent of dilution; and rU and rS are the peak responses for 2-ethyl-2-methylsuccinic acid obtained from the Test solution and the Standard solution, respectively: not more than 0.5% is found.
Mobile phase Prepare a filtered and degassed mixture of water, acetonitrile, and glacial acetic acid (875:125:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution Dissolve suitable quantities of USP Ethosuximide RS and 2-ethyl-2-methylsuccinic acid in Mobile phase to obtain a solution containing about 0.062 mg per mL and 0.064 mg per mL, respectively.
Standard preparation Dissolve an accurately weighed quantity of USP Ethosuximide RS in Mobile phase to obtain a solution having a known concentration of about 0.062 mg per mL.
Assay preparation Transfer 20 Capsules, accurately weighed, into a 2-liter volumetric flask, dissolve in 1800 mL of Mobile phase, dilute with Mobile phase to volume, and mix. Transfer 5.0 mL into a 200-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 225-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between ethosuximide and 2-ethyl-2-methylsuccinic acid is not less than 3.5; the tailing factor is not more than 1.5; and the relative standard deviations for replicate injections determined from ethosuximide and 2-ethyl-2-methylsuccinic acid are not more than 2.0% and 5.0%, respectively.
Procedure Separately inject equal volumes (about 10 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 ethosuximide (C7H11NO2) in the portion of each Capsule taken by the formula:
4000C(rU / rS)in which C is the concentration, in mg per mL, of USP Ethosuximide RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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