顶空气相色谱-质谱法测定依度沙班原料药中遗传毒性物质

Simultaneous Determination of the Contents of Genotoxicity Impurities in Edoxaban by Head-space GC-MS

目的建立内标法测定依度沙班原料药中遗传毒性杂质甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯的含量。方法采用顶空气相色谱-质谱法,以DB-WAX毛细管柱(30 m×0.25 mm,0.25μm)为色谱柱,程序升温,高纯氦气为载气,流速为0.6 m L·min^(-1),进样口温度为110℃,进样方式为分流进样,分流比为20∶1;顶空进样,平衡温度为60℃,平衡时间为30 min,进样体积1 m L;检测器为质谱检测器,离子源为EI源,离子源温度为200℃,接口温度为150℃,扫描方式为选择离子检测,电子能量为70 e V。结果甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯在0.05～3.0μg·m L^(-1)(r≥0.998 5)浓度范围内线性关系良好,加样回收率分别为96.4%,96.1%和96.5%,RSD分别为2.0%,1.9%,1.9%(n=6)。结论该方法简便、快速、灵敏度高、专属性好,可为依度沙班原料药的质量控制提供参考依据。

Objective To establish a method for the determination of the genotoxic impurities(methyl methanesulfonate,ethyl methanesulfonate and isopropyl methanesulfonate)in edoxaban with internal standard method.Methods A head-space GC-MS method was used.The column was DB-WAX capillary column(30m×0.25mm,0.25μm)by programmed temperature,carrier gas was high purity helium,column flow was0.6mL·min^-1,the inlet temperature was110℃,sample mode split injection with a split ratio of20:1;Head-space samp-ling was conducted,equilibrium temperature was60℃,equilibrium time was30min,injection volume was1mL;Detector was a mass spectrometer detector,the ion source was EI source and source temperature was200℃,the interface temperature was150℃,scanning method was selective ion monitoring,electron energy was70eV.Results The linear range of methyl methanesulfonate,ethyl methanesulfonate and isopropyl methanesulfonate were0.05-3.0μg·mL^-1(r≥0.9985);Recoveries were96.4%,96.1%and96.5%,respectively,and RSD were2.0%,1.9%and1.9%(n=6).Conclusion This method is simple,rapid,sensitive,with good specificity,and it can provide a reference for the quality control of edoxaban raw material with internal standard.