气相色谱法测定基因毒性杂质S-环氧氯丙烷  

Determination of Genotoxic Impurity S-epichlorohydrin by Gas Chromatography

作　　者：张洁 许建良 姚舒舒 Zhang Jie;Xu Jianliang;Yao Shushu(Nanjing Zhengda Tianqing Pharmaceutical Co.,Ltd.,Nanjing 210046,China)

机构地区：[1]南京正大天晴制药有限公司,江苏南京210046

出　　处：《广东化工》2023年第16期160-162,共3页Guangdong Chemical Industry

基　　金：国家市场监管总局科技计划项目(2020MK081)。

摘　　要：目的:建立气相色谱法测定利伐沙班起始物料中卤代烷烃类潜在基因毒性杂质S-环氧氯丙烷。方法:色谱柱Agilent DB-624(30 m×0.53 mm,3μm);升温程序起始温度40℃,以每分钟5℃的速率升温至140℃,维持3 min;进样口温度200℃;进样量10μL;分流比5∶1;柱流量3.0 mL/min;检测器温度:250℃。结果:杂质S-环氧氯丙烷质量浓度在5-20μg/mL范围内线性关系良好(r=0.9989),检测限为0.68μg/mL,定量限为2.27μg/mL,平均回收率为92.60%(RSD=5.0%,n=9),重复性良好(RSD=4.1%,n=6)。3批利伐沙班起始物料中未检出S-环氧氯丙烷。结论:经方法学验证,本法适用于利伐沙班起始物料中S-环氧氯丙烷的测定。Objective:To establish a gas chromatographic method for the determination of potential genotoxic impurity S-epichlorohydrin in rivaroxaban starting material.Methods:The chromatographic column was Agilent DB-624(30 m×0.53 mm,3μm).The initial temperature of the heating program is 40℃,and the temperature rises to 140℃at a rate of 5℃per minute for 3 minutes.Inlet temperature 200℃;Injection volume 10μL;Split ratio 5∶1;Column flow rate 3.0 mL/min;Temperature of detector:250℃.Results:The concentration of S-epichlorohydrin in the range of 5~20μg/mL had a good linearity(r=0.9989),the limit of detection was 0.68μg/mL,the limit of quantification was 2.27μg/mL,the average recovery was 92.60%(RSD=5.0%,n=9).The repeatability was good(RSD=4.1%,n=6).No S-epichlorohydrin was detected in three batches of rivaroxaban starting material.Conclusion:The method is suitable for the determination of S-epichlorohydrin in rivaroxaban starting material.

关 键 词：利伐沙班 卤代烷烃类杂质 潜在基因毒性杂质 S-环氧氯丙烷 (S)-(+)-N-(2 3-乙氧基丙基)邻苯二甲酰亚胺 气相色谱法 

分 类 号：TQ[化学工程]