Determination of the Related Substances in Clopidogrel Bisulfate Aspirin Tablets by HPLC

OBJECTIVE To establish an HPLC method for determining the contents of the related substances in clopidogrel bisulfate aspirin tablets. METHODS The chromatographic analysis was performed on Waters XBridge Shield RP₁₈ column(250 mm×4.6 mm, 5 μm) with 0.1% triethylamine(adjusted with phosphoric acid to pH 2.5±0.1) and methanol as mobile phase using gradient elution at a flow rate of 1.0 mL·min⁻¹. The UV detection wavelength was 220 nm. RESULTS Clopidogrel bisulfate, aspirin and relate substances were well separated. The calibration curves were linear in the range of 0.59-178.32 μg·mL^-1 for aspirin impurity C(r=0.999 9), 0.31-12.47 μg·mL^-1 for aspirin impurity D(r=1.000 0), 0.33- 13.21 μg·mL^-1 for aspirin impurity E(r=0.999 8), 0.31-18.49 μg·mL^-1 for aspirin impurity F(r=0.999 7), and 0.76- 30.28 μg·mL^-1 for clopidogrel bisulfate impurity A(r=0.999 9), respectively. The average recoveries of aspirin impurity C, impurity D, impurity E, impurity F and clopidogrel bisulfate impurity A were 97.47%, 102.16%, 102.20%, 103.71% and 104.16% respectively, the RSDs were 5.35%, 1.93%, 1.40%, 4.63% and 2.45% respectively. CONCLUSION The method is simple, accurate, reliable, and can be used for the quality control of the related substances in clopidogrel bisulfate aspirin tablets.