GC-MS测定地氯雷他定中基因毒性杂质氯甲酸乙酯的含量

目的 建立地氯雷他定中基因毒性杂质氯甲酸乙酯含量的GC-MS方法。方法 采用CNW CD-ACIDWAX色谱柱（30 m×0.25 mm，0.25 μm）进行分离，载气为氦气，气体流速为1.2 mL·min^-1。通过20∶1分流顶空进样，顶空温度为70℃，程序升温：50℃柱温箱条件下保持5 min，再以10℃·min^-1升温至80℃，保持3 min。在SIM扫描方式下，检测氯甲酸乙酯的含量，定量离子为m/z 63。结果 氯甲酸乙酯浓度在0.05~4.00μg·mL^-1内线性良好，分析方法的重复性、中间精密度、回收率、溶液稳定性、耐用性等均在相关验证指导原则的规定范围内。结论 该定量方法准确、可靠、重复性好，可用于地氯雷他定原料药中氯甲酸乙酯的杂质检测。

Content Determination of Genotoxic Impurity Ethyl Chloroformate in Desloratadine by GC-MS

OBJECTIVE To develop the GC-MS quantitative method for genotoxic impurity ethyl chloroformate in desloratadine. METHODS CNW CD-ACIDWAX(30 m×0.25 mm, 0.25 μm) column was used with the helium as the carrier gas, the gas flow rate was set at 1.2 mL·min^-1. Through 20:1 split head space injection, the headspace temperature was set at 70℃. The temperature was programmed by holding it for 5 min in a column temperature chamber at 50℃ and then heat up to 80℃ at a rate of 10℃·min^-1, and kept at 80℃ for 3 min. Determined by SIM mode, the quantitative ion of ethyl chloroformate was m/z 63. RESULTS The calibration curve of ethyl chloroformate showed good linearity within the concentration range of 0.05-4.00 µg·mL^-1. All the validation parameters about the method including repeatability, intermediate precision, accuracy, solution stability and durability met the required acceptance of relevant method validation guidance. CONCLUSION The method is accurate, reliable and reproducible, and it is suitable for the determination of ethyl chloroformate in desloratadine.