GC-MS法测定塞来昔布中硫酸酯类基因毒性杂质

Determination of Sulfates of Genotoxic Impurities in Celecoxib by GC-MS

目的 建立GC-MS方法测定塞来昔布中硫酸酯类基因毒性杂质硫酸二甲酯、硫酸二乙酯、硫酸二异丙酯的含量。方法 色谱柱为Agilent DB^(-1)7MS (30 m×0.25 mm,0.25μm);进样口温度为200℃;载气为高纯氦气,流速为1.5 m L·min^(-1);进样方式为直接进样,进样体积为1μL;分流比为20∶1。离子源为EI源,离子源温度为260℃,电离能量70 e V;采集模式为选择性离子监测(SIM)。结果 硫酸二甲酯、硫酸二乙酯、硫酸二异丙酯在0.06~3.0μg·m L^(-1)范围内线性关系良好(n=6),相关系数均大于0.998;硫酸二甲酯、硫酸二乙酯、硫酸二异丙酯的平均回收率分别为99.81%、100.66%、100.34%,回收率的RSD分别为1.36%、0.81%、1.33%。加样对照溶液在24 h内稳定。结论 该方法高效、准确、灵敏度高,可以用于塞来昔布中基因毒性杂质硫酸二甲酯、硫酸二乙酯、硫酸二异丙酯的测定。

OBJECTIVE To establish a GC-MS method for the determination of sulfates of genotoxic impurities in Celecoxib.METHODS An DB^(-1)7MS column( 30 m × 0.25 mm,0.25 μm) was adopted for separation with a injector temperature of 200 ℃.Helium as used as the carrier gas,and The carrier gas flow rate was set at 1.5 m L·min^(-1)with a split ratio of 20 ∶ 1.The injection method was direct injection,and the injection volume was 1 μL.The ion source was EI source,the ion source temperature was 260 ℃,and the ionization energy was 70 eV;The acquisition mode was selective ion monitoring( SIM).RESULTS The linear relationship in the range of 0.06-3.0 μg·m L^(-1)was good( n = 6).The assay of dimethyl sulfate,diethyl sulfate and diisopropyl sulfate were linear over the certain range( r > 0.998).The average recoveries of dimethyl sulfate,diethyl sulfate and diisopropyl sulfate were99.81%,100.66% and 100.34% with RSD of 1.36%,0.81% and 1.33%.The sample control solution had good stability within 24 h at room temperature.CONCLUSION The method is efficient,accurate and sensitive,and can be used for the determination of genotoxic impurities dimethyl sulfate,diethyl sulfate and diisopropyl sulfate in Celecoxib.