A:Infrared Absorption á197Kñ.

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.

C: It responds to the test for Sulfate á191ñ.

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

Standard solution— Dissolve accurately weighed quantities of USP Clopidogrel Related Compound A RS,USP Clopidogrel Related Compound B RS,and USP Clopidogrel Related Compound C RSin methanol,and dilute with methanol to obtain a solution having concentrations of about 0.1,0.4,and 0.3mg per mL,respectively.Dilute this solution with Mobile phase,and mix to obtain a solution having final concentrations of about 10,40,and 30µg per mL,respectively.

Test solution— Transfer about 100mg of Clopidogrel Bisulfate,accurately weighed,to a 200-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.

Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solution into the chromatograph,record the chromatograms,and measure the areas for all the peaks.Calculate the percentage of related compounds in the portion of Clopidogrel Bisulfate taken by the formula: in which CSis the concentration,in mg per mL,of relevant USP Clopidogrel Related Compound RSin the Standard solution;CTis the concentration,in mg per mL,of Clopidogrel Bisulfate in the Test solution;rUis the peak response for clopidogrel related compound obtained from the Test solution;and rSis the peak response for relevant clopidogrel related compound obtained from the Standard solution:not more than 0.2%of clopidogrel related compound Ais found;not more than 0.3%of clopidogrel related compound Bis found;not more than 1.0%of clopidogrel related compound Cis found;not more than 0.1%of any other impurity is found;and not more than 1.5%of total impurities is found.

Phosphate buffer— Dissolve 1.36g of monobasic potassium phosphate in about 500mLof water,and dilute with water to 1000mL.

Mobile phase— Prepare a filtered and degassed mixture of Phosphate buffer and acetonitrile (75:25).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard stock solution— Transfer about 100mg of USP Clopidogrel Bisulfate RS,accurately weighed,to a 100-mLvolumetric flask.Dissolve in and dilute with methanol to volume,and mix.

Standard preparation— Dilute a suitable portion of Standard stock solution,accurately measured,with Mobile phaseto obtain a solution having a known concentration of about 0.1mg per mL.

System suitability solution— Dissolve an accurately weighed quantity of USP Clopidogrel Related Compound B RSin methanol,and mix with a suitable portion of Standard stock solution,to obtain concentrations of about 1.0and 0.5mg per mL,respectively.Dilute this solution with Mobile phase,and mix to obtain a solution having a final concentration of about 0.05mg per mLof clopidogrel bisulfate and about 0.1mg per mLof clopidogrel related compound B.

Assay preparation— Transfer about 100mg of Clopidogrel Bisulfate,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.Pipet 5.0mLof this solution to a 50-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 4.6-mm ×15-cm column that contains packing L57(see Chromatography á621ñ).The flow rate is about 1.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.8and 1.2for enantiomers of clopidogrel related compound B,respectively,and 1.0for clopidogrel;and the resolution,R,between clopidogrel and the first enantiomer of clopidogrel related compound Bis not less than 2.5.Chromatograph the Standard preparation:the relative standard deviation for replicate injections determined from clopidogrel bisulfate is not more than 1.0%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for all the peaks.Calculate the quantity,in mg,of C16H16ClNO2S·H2SO4in the portion of Clopidogrel taken by the formula: in which Cis the concentration,in mg per mL,of USP Clopidogrel Bisulfate RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.