UPLC-MS-MS法测定原料药中对甲苯磺酸酯类遗传毒性杂质

Determination of P-toluenesulfonic Acid Esters Impurities in API by UPLC-MS/MS

建立超高效液相色谱-串联质谱法(UPLC-MS/MS)测定硫酸氢氯吡格雷中对甲苯磺酸甲酯和对甲苯磺酸乙酯。以0.1%甲酸水-乙腈为流动相进行线性梯度洗脱。采用ESI离子源正离子模式,多反应监测模式下以外标法对2种遗传毒性杂质进行定量测定。2种遗传毒性杂质质量浓度在5.0~200.0 ng·mL^-1范围内线性关系良好;低中高加标回收率(n=3)为94.1%~105.3%,RSD为1.7%~4.4%。本方法操作简便,结果可靠,可用于硫酸氢氯吡格雷中对甲苯磺酸酯类遗传毒性杂质的检测。

An UPLC-MS/MS analytical method for the determination of genotoxic impurities(methyl p-toluenesulfonate and ethyl p-toluenesulfonate)in clopidogrel bisulfate was established.The separation was performed with the mobile phase consisting of 0.1%formic acid aqueous solution and acetonitrile.Multiple reaction monitoring(MRM)was performed on a triple quadrupole mass spectrometer equipped with a ESI source in the positive mode.The calibration curve was linear for other compounds in the range of 5.0~200.0 ng·mL^-1.The recoveries(n=3)of adding concentrations were 94.1%~105.3%,RSD were 1.7%~4.4%.The established method is simple,rapid and reliable,which is applicable for both quantification of two genotoxic impurities in in clopidogrel bisulfate.