Ethosuximide Capsules
»Ethosuximide Capsules contain not less than 93.0percent and not more than 107.0percent of the labeled amount of C7H11NO2,present in the form of a solution of Ethosuximide in Polyethylene Glycol 400or other suitable solvent.
Packaging and storage— Preserve in tight containers.
Identification— Place a portion of the Capsule contents,equivalent to about 300mg of ethosuximide,in a separator containing 50mLof ether.Shake with three 10-mLportions of water,discarding the aqueous extracts.Add about 5g of anhydrous sodium sulfate,swirl for 3minutes,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 5mLof chloroform:the IRabsorption spectrum of the solution,in the region between 3000cm-1and 1650cm-1,determined in a 0.1-mm cell,exhibits maxima only at the same wavelengths as that of a 1in 15solution of USP Ethosuximide RSin chloroform.
Dissolution,Procedure for a Pooled Sample á711ñ—
Medium: pH6.8phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions);900mL.
Apparatus 1: 50rpm.
Time: 30minutes.
Mobile phase— Prepare a degassed and filtered mixture of water and acetonitrile (80:20).
Chromatographic system (see Chromatography á621ñ)— 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 1.5mLper 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 50µL)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 C7H11NO2dissolved by comparison with a Standard solution,having a known concentration of USP Ethosuximide RSin the same Medium,similarly chromatographed.
Tolerances— Not less than 80%(Q)of the labeled amount of C7H11NO2is dissolved in 30minutes.
Uniformity of dosage units á905ñ: 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 0.026mg per mL.
Test solution— Transfer 20Capsules into a 2-liter volumetric flask,dissolve in 1800mLof Mobile phase,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 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 CSis the concentration,in mg per mL,of 2-ethyl-2-methylsuccinic acid in the Standard solution;CUis 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 rUand rSare the peak responses for 2-ethyl-2-methylsuccinic acid obtained from the Test solutionand the Standard solution,respectively:not more than 0.5%is found.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of water,acetonitrile,and glacial acetic acid (875:125:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution— Dissolve suitable quantities of USP Ethosuximide RSand 2-ethyl-2-methylsuccinic acid in Mobile phaseto obtain a solution containing about 0.062mg per mLand 0.064mg per mL,respectively.
Standard preparation— Dissolve an accurately weighed quantity of USP Ethosuximide RSin Mobile phaseto obtain a solution having a known concentration of about 0.062mg per mL.
Assay preparation— Transfer 20Capsules,accurately weighed,into a 2-liter volumetric flask,dissolve in 1800mLof Mobile phase,dilute with Mobile phaseto volume,and mix.Transfer 5.0mLinto a 200-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— 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 1mLper 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 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 ethosuximide (C7H11NO2)in the portion of each Capsule taken by the formula:
4000C(rU/rS),
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.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 793
Pharmacopeial Forum:Volume No.30(1)Page 102
Phone Number:1-301-816-8165