A: Infrared Absorption á197Sñ—

pH3.0Phosphate buffer,Mobile phase,System suitability solution,andChromatographic system— Proceed as directed in the Assay.

Standard solution— Dissolve accurately weighed quantities of USP Ethosuximide RSand 2-ethyl-2-methylsuccinic acid in Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 0.1mg of each per mL.

Test solution— Transfer about 1g of Ethosuximide,accurately weighed,into a 10-mLvolumetric flask,dissolve in Mobile phase,sonicating if necessary,dilute with Mobile phaseto volume,and mix.

Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for all the peaks with an area greater than 0.1%of the total area,except the ethosuximide peak.Calculate the percentage of 2-ethyl-2-methylsuccinic acid in the portion of Ethosuximide taken by the formula: in which Cis the concentration,in mg per mL,of 2-ethyl-2-methylsuccinic acid in the Standard solution;Wis the weight,in g,of Ethosuximide taken to prepare the Test solution;and riand rSare the peak responses of 2-ethyl-2-methylsuccinic acid obtained from the Test solutionand the Standard solution,respectively:not more than 0.1%is found.Calculate the percentage of any other impurity in the portion of Ethosuximide taken by the formula: in which Cis the concentration,in mg per mL,of USP Ethosuximide RSin the Standard solution;Wis the weight,in g,of Ethosuximide taken to prepare the Test solution;riis the peak response for each impurity obtained from the Test solutionother than 2-ethyl-2-methylsuccinic acid;and rSis the peak response for ethosuximide obtained from the Standard solution:not more than 0.1%of any other impurity is found;and not more than 0.5%of total impurities is found.

pH3.0Phosphate buffer— Add 4.1mLof phosphoric acid to 1000mLof water,and adjust with sodium hydroxide TSto a pHof 3.0.

Mobile phase— Prepare a filtered and degassed mixture of pH3.0Phosphate bufferand acetonitrile (90:10).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

System suitability solution— Dissolve suitable quantities of 2-ethyl-2-methylsuccinic acid and USP Ethosuximide RSin an appropriate volume of Mobile phaseto obtain a solution containing about 2mg per mLand 10mg per mL,respectively.

Standard preparation— Dissolve an accurately weighed quantity of USP Ethosuximide RSin Mobile phase,and dilute with Mobile phaseto obtain a solution having a known concentration of about 10.0mg per mL.

Assay preparation— Transfer about 100mg of Ethosuximide to a 10-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm ×30.0-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between 2-ethyl-2-methylsuccinic acid and ethosuximide is not less than 6.6;the column efficiency determined from ethosuximide is not less than 2900theoretical plates;the tailing factor for the ethosuximide peak is not more than 2.0;and the relative standard deviation for replicate injections is not more than 0.4%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C7H11NO2in the portion of Ethosuximide taken by the formula: in which Cis the concentration,in mg per mL,of USP Ethosuximide RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.