LC-MS/MS法测定盐酸吉西他滨中磺酸酯类基因毒杂质

Study on LC-MS/MS method for determination of genotoxic impurities ate in gemcitabine hydrochloride

建立LC-MS/MS法检测盐酸吉西他滨中基因毒性杂质甲磺酸甲酯和甲磺酸乙酯的方法.选用C18色谱柱(以十八烷基硅烷键合硅胶为填充剂,150 mm×4.6mm,5μm),以甲醇-水(体积比30∶70)为流动相,流速为1.0 m L/min,分流比为30%,柱温为40℃,进样量为10μL.采用APCI离子源检测扫描方式负离子模式检测.结果甲磺酸甲酯和甲磺酸乙酯质量浓度在20~200μg/L内与峰面积线性关系良好,甲磺酸甲酯和甲磺酸乙酯的检测限为4μg/L,定量限为10μg/L.本方法灵敏、专属性强,适用于盐酸吉西他滨中基因毒性杂质甲磺酸甲酯和甲磺酸乙酯的检测.

To establish a convenient LC-MS/MS analytical method for the determination of genotoxic impurities including methyl methanesulfonate and ethyl methanesulfonate in 2-deoxy-D-ribose. The analysis was performed on C18（ 150 mm × 4. 6 mm,5 μm） column maintained at 40 ℃ with a mobile phase of methanol-water（ V∶ V = 30∶ 70）. The flow rate was 1. 0 m L/min. The split ratio was 30% and 10 μL sample solution was injected into the LC-MS/MS system. Detection of the reference solution and the sample solution was carried out by APCI on a TSQ Quantum Ultra LC-MS/MS system. The assay of methyl methanesulfonate and ethyl methanesulfonate was linear over the range 20 - 200 μg/L,with a limit of detection of 4 μg/L and with a limit of quantitation of 10 μg/L. The method was rapid,sensitive,selective,and reliable for the determination of genotoxic impurities including methyl methanesulfonate and ethyl methanesulfonate in gemcitabine hydrochloride.