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

关键词:  硫酸氢氯吡格雷阿司匹林片  高效液相色谱法  有关物质

Key words:  clopidogrel bisulfate aspirin tablets  HPLC  related substances

摘要:

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，5 μm），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0.999 9，1.000 0，0.999 8，0.999 7和0.999 9。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。

Abstract:

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.