HPLC 测定硫酸氢氯吡格雷阿司匹林片有关物质

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

目的建立HPLC测定硫酸氢氯吡格雷阿司匹林片有关物质。方法采用Waters XBridge Shield RP18色谱柱(250 mm×4.6 mm,5μm),以0.1%三乙胺溶液(用磷酸调节pH值至2.5±0.1)-甲醇为流动相进行梯度洗脱,流速为1.0 mL·min^-1,检测波长为220 nm。结果各杂质与主峰之间的分离度良好,阿司匹林杂质C、D、E、F及氯吡格雷杂质A浓度分别在0.59~178.32,0.31~12.47,0.33~13.21,0.31~18.49和0.76~30.28μg·mL^-1内与峰面积呈良好的线性关系,r分别为0.9999,1.0000,0.9998,0.9997和0.9999。阿司匹林杂质C、D、E、F及氯吡格雷杂质A加样回收率的平均值分别为97.47%,102.16%,102.20%,103.71%和104.16%,RSD分别为5.35%,1.93%,1.40%,4.63%和2.45%。结论本方法简便、准确可靠,适用于硫酸氢氯吡格雷阿司匹林片中有关物质的控制。

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,5μm)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 0.59-178.32μg·mL^-1 for aspirin impurity C(r=0.9999),0.31-12.47μg·mL^-1 for aspirin impurity D(r=1.0000),0.33-13.21μg·mL^-1 for aspirin impurity E(r=0.9998),0.31-18.49μg·mL^-1 for aspirin impurity F(r=0.9997),and 0.76-30.28μg·mL^-1 for clopidogrel bisulfate impurity A(r=0.9999),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.