UPLC-MS/MS法测定酮咯酸氨丁三醇中的一种基因毒性杂质  

A genotoxic impurity in ketorolac tromethamine determined by UPLC-MS/MS

作　　者：侯继鹏 时晓燕 张业华 王凯 郝贵周 张贵民 HOU Ji-peng;SHI Xiao-yan;ZHANG Ye-hua;WANG Kai;HAO Gui-zhou;ZHANG Gui-min(National Engineering Research Center of Chiral Drugs,Lunan Pharmaceutical Group Co.,Ltd.,Linyi Shandong 273400)

机构地区：[1]鲁南制药集团股份有限公司,国家手性制药工程技术研究中心,山东临沂273400

出　　处：《中南药学》2023年第9期2424-2427,共4页Central South Pharmacy

摘　　要：目的建立UPLC-MS/MS法测定酮咯酸氨丁三醇中的基因毒性杂质2-[4-苯甲酰基-1-(2-氯乙基)-1H-吡咯-2-基]乙酸乙酯。方法色谱柱采用ACQUITY BEH C18柱(2.1 mm×50 mm,1.7μm),流动相为0.1%甲酸溶液-乙腈(60∶40),等度洗脱。采用电喷雾电离源(ESI),正离子模式采集,多反应监测(MRM)模式。结果2-[4-苯甲酰基-1-(2-氯乙基)-1H-吡咯-2-基]乙酸乙酯在0.0771~1.5410 ng·mL^(-1)内与峰面积线性关系良好,平均回收率在104.4%~108.2%,RSD均小于5%。定量限与检测限分别为0.0771、0.0231 ng·mL^(-1)。结论建立的方法准确、简便、快速、灵敏度高、专属性强,能有效测定酮咯酸氨丁三醇中2-[4-苯甲酰基-1-(2-氯乙基)-1H-吡咯-2-基]乙酸乙酯的含量,为酮咯酸氨丁三醇的质量控制提供参考。Objective To determine genotoxic impurity 2-[4-benzoyl-1-(2-chloroethyl)-1H-pyrrol-2-yl]ethyl acetate in ketorolac tromethamine by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Methods The ACQUITY BEH C18 column(2.1 mm×50 mm,1.7μm)was used,and the analysis was conducted in the isocratic elution mode with 0.1%formic acid solutionacetonitrile(60∶40)as the mobile phase.Electron spray ionization(ESI),positive ion mode acquisition and multiple reaction monitoring(MRM)mode were used.Results It was linear for 2-[4-benzoyl-1-(2-chloroethyl)-1H-pyrrol-2-yl]ethyl acetate at 0.0771~1.5410 ng·mL^(-1),and the average recovery was 104.4%~108.2%,with RSD<5%.The quantification limit and the detection limit were 0.0771 and 0.0231 ng·mL^(-1),respectively.Conclusion The method is accurate,simple,rapid,sensitive and specific,which can effectively determine the 2-[4-benzoyl-1-(2-chloroethyl)-1H-pyrrol-2-yl]ethyl acetate in ketorolac tromethamine,and provide a reference for the quality control of ketorolac tromethamine.

关 键 词：酮咯酸氨丁三醇 基因毒性杂质 2-[4-苯甲酰基-1-(2-氯乙基)-1H-吡咯-2-基]乙酸乙酯 超高效液相色谱-串联质谱 

分 类 号：R927[医药卫生—药学]