GC-MS法测定甲巯咪唑原料药中异硫氰酸甲酯和2-氯乙醛缩二乙醇的浓度

Determination of methyl-isothiocyanate and 2-chloroacetaldehyde diethyl acetal in thiamazole raw material by GC-MS

目的建立一种测定甲巯咪唑原料药中异硫氰酸甲酯和2-氯乙醛缩二乙醇浓度的GC-MS方法.方法用DB-624毛细管柱(30.00 m×0.32 mm,1.80μm),程序升温,进样口温度170℃,分流比10:1,流速1.0 mL·min^(-1).接口温度280℃,离子源温度250℃,四极杆温度150℃.用电子轰击离子化(EI源)电离方式,电子能量70 eV,选择离子检测(SIM)模式.考察该方法的专属性、标准曲线与定量下限、精密度与回收率,以及稳定性.结果异硫氰酸甲酯和2-氯乙醛缩二乙醇的线性范围均为0.1~10.0μg·mL^(-1),相关系数均≥0.9989,定量下限均为0.06μg·mL^(-1),日内精密度分别为1.44%和4.34%,日间精密度分别为2.42%和2.52%,平均回收率均不低于93.61%,稳定性结果良好,RSD为1.90%.结论本方法简便、快速、灵敏度高、专属性好,可为甲巯咪唑原料药中异硫氰酸甲酯和2-氯乙醛缩二乙醇质量控制提供参考依据.

Objective To establish a method for the determination of genotoxic impurities including methyl-isothiocyanate and 2-chloroacetaldehyde diethyl acetal in thiamazole raw material by GC-MS.Methods For separation,DB-624(30.00 mm×0.32 mm,1.80μm)capillary column and an temperature program were applied.The injection port temperature was 170℃,flow rate:1.0 mL·min^(-1),split ratio:10∶1.Under the SIM ion detection mode,an electron impact ionization(EI)with 70 eV electron energy was adopted for determination.The interface temperature was 280℃,ion source temperature:250℃,quadrupole temperature:150℃.Methodological validation including specificity,standard curve,lower limit of quantification,precision,recovery were investigated.Results The linear ranges of methyl-isothiocyanate and 2-chloroacetaldehyde diethyl acetal were all 0.1-10.0μg·mL^(-1)(r≥0.9989);lower limits of quantification were 0.06μg·mL^(-1),respectively.The intra-day and inter-day precisions were less than 4.34%and the average recoveries were larger than 93.61%.Good stability was obtained with RSD=1.90%.Conclusion The method is simple,rapid,sensitive with good specificity.The method provided a reference for the quality control of genotoxicity impurities methyl-isothiocyanate and 2-chloroacetaldehyde diethyl acetal in thiamazole raw material.