GC-MS法测定奥拉西坦原料中的潜在遗传毒性杂质  

Determination of the Potential Genotoxic Impurities in Oxiracetam Raw Material by GC-MS

作　　者：朱雪萍 仰凡 焦伟 王枫 吴小明 

机构地区：[1]南京优科制药有限公司,南京210029 [2]江苏国创环保科技有限公司

出　　处：《中国药师》2018年第1期174-176,共3页China Pharmacist

摘　　要：目的:建立同时测定奥拉西坦原料药中潜在遗传毒性杂质氯乙酸甲酯和(R,S)4-氯-3-羟基丁酸乙酯的方法。方法:采用GC-MS法,使用乙酸乙酯进行提取。色谱柱为VF^(-1)701 ms毛细管柱(30 m×0.25 mm,0.25μm),柱温采用程序升温,进样口温度为220℃,柱流量为1.0 ml·min^(-1),吹扫流量为5.0 ml·min^(-1),进样方式为分流进样,分流比为5∶1,载气为高纯氦气,检测器为MS检测器,离子源温度为230℃,接口温度为230℃,溶剂延迟时间为4 min,离子化模式为电子轰击离子化模式,扫描(检测)方式为选择性离子检测,电子能量为70 e V,进样量为1.0μl。结果:2种杂质成分之间的分离度符合要求,浓度线性范围均为50~400 ng·ml^(-1)(r≥0.999 5),加样回收率分别为89.7%~96.3%(RSD=2.3%,n=9)、91.0%~105.3%(RSD=4.4%,n=9)。结论:该方法简便、准确、灵敏、迅速,可用于奥拉西坦原料药中2种潜在遗传毒性杂质的测定。Objective： To establish a method for the determination of the potential genotoxic impurities [ methyl chloroacetate and （R, S） 4-ethyl chloro-3-hydroxybutyrate] in oxiracetam raw material. Methods： GC-MS was conducted, and the potential genotoxic impurities were extracted by ethyl acetate. The column was a VF-1701 ms capillary column （30 m ×0.25mm,0.25μm） with pro- grammed temperature and the inlet temperature was 220 ℃. The column flow was 1.0 ml min-1 and the purge flow was 5.0 ml min-1 . The split injection was used and the split ratio was 5： 1. The carder gas was high purity helium and the detector was a mass spectrometer detector. The ion source temperature was 230 ℃ and the interface temperature was 230℃. The delay time of solvent was 4 min and the ionization mode was electron impact. The scanning（detection） method was selective ion monitoring, the electron energy was 70 eV, and the injection volume was 1.0 μl. Results： The separation between the impurities met the requirements. The concen- tration linear range was 50-400 ng ml-1 （r≥0.999 5）. The recoveries were 89.7%-96.3% （RSD =2.3%, n =9） and 91.0%- 105.3% （RSD = 4.4%, n = 9）, respectively. Conclusion： The method is simple, accurate, sensitive and rapid, and can be used for the determination of two potential genotoxic impurities in oxiracetam raw material.

关 键 词：奥拉西坦原料药 潜在遗传毒性杂质 氯乙酸甲酯 (R S)4-氯-3-羟基丁酸乙酯 气相色谱-质谱联用法 

分 类 号：TQ460.72[医药卫生—药物分析学]