摘要
目的:建立一种气质联用色谱检测左乙拉西坦中基因毒性杂质4-氯丁酸甲酯和4-氯丁酸乙酯含量mL·min-1;进样方式用分流进样,分流比2∶1;载气为氦气;检测器为质谱检测器;离子化方式为EI;溶剂延甲酯和4-氯丁酸乙酯的检测;4-氯丁酸甲酯和4-氯丁酸乙酯在一定范围内线性良好,r均大于0.990 0;定量下限分别为0.979 7、1.789 ng·mL^-1;加样回收率良好,平均加样回收率(n=12)分别为93.9%,90.9%;RSD灵敏度高,专属性和准确度好,可用于左乙拉西坦中4-氯丁酸甲酯和4-氯丁酸乙酯检测。
Objective:To establish a gas chromatography-mass spectrometry(GC-MS)method for the determination of two genotoxic impurities methyl 4-chlorobutyrate and ethyl 4-chlorobutyrate in levetiracetam.Methods:An HP-INNOWAX(30 m×0.25 mm,0.25 μm)column was adopted for separation;injector temperature was 220 ℃;the flow rate of carrier gas-helium was 1.0 mL·min-1;the split ratio was 2∶1;the time of solvent delay was 5 minutes;EI,selected ion monitor(SIM)and external standard method were used in MS analysis.Results:Blank solvent or levetiracetam showed no interference.The assay of methyl 4-chlorobutyrate and ethyl 4-chlorobutyrate were linear over the certain range(r>0.990).Limit of quantitation(LOQ)were 0.979 7 ng·mL^-1, 1.789 ng·mL^-1,respectively.The average recoveries of methyl 4-chlorobutyrate and ethyl 4-chlorobutyrate were 93.9% and 90.9%,with RSD 2.4% and 6.0%.The control solution and the labeled sample solution were stable after 28.5 h and 24.5 h at room temperature.Conclusion:The method is sensitive,selective,and accurate.It can be used to detect genotoxic impurities methyl 4-chlorobutyrate and ethyl 4-chlorobutyrate in levetiracetam.
作者
赵晓亚
李宜玲
薛志旗
刘清梁
ZHAO Xiao-ya;LI Yi-ling;XUE Zhi-qi;LIU Qing-liang(Research and Development center of China Resources Saike Pharmaceutical Co.,Ltd.Beijing 101111,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2020年第12期2167-2173,共7页
Chinese Journal of Pharmaceutical Analysis
