UPLC-MS/MS法测定对甲苯磺酸-2-噻吩乙酯中对甲苯磺酰氯的含量  

Determination of p-toluenesulfonyl chloride in 2-(2-thienyl) ethyl p-toluenesulfonate by using UPLC-MS/MS

作　　者：刘卓霖 姬巍 薛英 刘万卉[1,2] LIU Zhuo-lin;JI Wei;XUE Ying;LIU Wan-hui(School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China;State Key Laboratory of Long-acting and Targeting Drug Delivery System,Luye Pharma Group Ltd.,Yantai 264003,China)

机构地区：[1]烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心,分子药理和药物评价教育部重点实验室(烟台大学),烟台264005 [2]绿叶制药集团有限公司长效和靶向制剂国家重点实验室,烟台264003

出　　处：《药物分析杂志》2020年第11期2056-2061,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:采用衍生化方法,建立超高效液相色谱-三重四极杆质谱联用方法(UPLC-MS/MS)测定对甲苯磺酸-2-噻吩乙酯中基因毒性杂质对甲苯磺酰氯的含量。方法:采用Agilent EclipsePlus C18(2.1mm×50 mm,1.8μm)色谱柱,以0.1%甲酸溶液-乙腈(50∶50)为流动相,流速为0.4 mL·min^-1。以0.3%苯胺乙腈溶液为衍生化试剂,对对甲苯磺酰氯进行衍生化前处理。在质谱电喷雾(ESI)正离子模式下检测,采用多反应监测(MRM)扫描模式,选择m/z 248.1→93.2作为定量离子对,m/z 248.1→156.1作为定性离子对。结果:对甲苯磺酰氯在0.18~360.0 ng·mL^-1范围内线性关系良好,r=0.9998;检测下限为0.06ng·mL^-1,定量下限为0.18 ng·mL^-1;低、中、高浓度平均回收率分别为96.4%、97.0%、95.5%,RSD分别为0.75%、0.32%、0.57%(n=3);3批样品中对甲苯磺酰氯的含量分别为0.09、0.55、1.19 ng·mg-1。结论:该方法准确可靠,可用于对甲苯磺酸-2-噻吩乙酯中对甲苯磺酰氯的含量检测。Objective:To establish a derivatization method for determination of p-toluenesulfonyl chloride as a genotoxic impurity in 2-(2-thienyl)ethyl p-toluenesulfonate by using UPLC-MS/MS.Methods:The separation was performed on the EclipsePlus C18(2.1 mm×50 mm,1.8μm)column with 0.1%formic acid aqueous solution as mobile phase A and acetonitrile as mobile phase B by isocratic elution for velocity of 0.4 mL·min^-1,p-toluenesulfonyl chloride was treated with derivatization reagent mixing 0.3%aniline in acetonitrile solution before processing.Multiple reaction monitoring(MRM)was selected in mass spectrometry with the ESI source in positive ion mode,and scanning in m/z 248.1→93.2 as quantitative ion pair and in m/z 248.1→156.1 as qualitative ion pair.Results:The calibration curve of p-toluenesulfonyl chloride derivatives was good linear within the range of 0.18-360.0 ng·mL^-1(r=0.9998).The minimum detection limit was 0.06 ng·mL^-1,and the minimum quantitative limit was 0.18 ng·mL^-1.The average recoveries of low,medium,and high concentration were 96.4%,97.0%,95.5%with RSDs of 0.75%,0.32%,0.57%(n=3),respectively.The contents of p-toluenesulfonyl chloride in the three batches were 0.09,0.55 and 1.19 ng·mg-1,respectively.Conclusion:The derivatization method for determination of p-toluenesulfonyl chloride in 2-(2-thienyl)ethyl p-toluenesulfonate by using UPLC-MS/MS is suitable and sensitive.

关 键 词：超高效液相-质谱联用 衍生化法 基因毒性杂质 定量分析 对甲苯磺酰氯 对甲苯磺酸-2-噻吩乙酯 

分 类 号：R917[医药卫生—药物分析学]