HPLC-QTOFMS法测定马来酸依那普利及中间体中的对甲苯磺酸乙酯  

HPLC-QTOF MS determination of ethyl p-toluenesulfonate in enalapril maleate and its intermediate

作　　者：宋冬梅[1,2] 徐倩昱[1] 任美婷[2] 段更利[1] 

机构地区：[1]上海复旦大学,上海201203 [2]上海市食品药品检验所,上海201203

出　　处：《药物分析杂志》2012年第5期834-837,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立HPLC-QTOF MS测定马来酸依那普利及中间体N-[1-(S)-乙氧甲酰基-3-苯丙基]-L-丙氨酸中对甲苯磺酸乙酯的方法。方法:采用Eclipse plus C18色谱柱(3.0 mm×100 mm,1.8μm),以20 mmol·L-1甲酸铵水溶液(A)-乙腈(B)为流动相,梯度洗脱(0～2 min,10%→50%B;2～4 min,50%→60%B;4～7 min,60%→90%B;7～8 min,90%B),流速1.0 mL·min-1,柱温50℃;采用正离子模式采集数据。结果:对甲苯磺酸乙酯浓度在0.20～5.01μg.mL-1范围内线性关系良好(r=0.9955);日内和日间精密度良好,RSD小于6.7%;定量限和检测限分别为0.4 ng、0.2 ng;马来酸依那普利及中间体回收率(n=9)分别为102.6%和90.8%。结论:本法简便、灵敏,可用于对甲苯磺酸乙酯的定量研究。Objective：To establish a method of HPLC-QTOF MS to detect ethyl p-toluenesulfonate in enalapril maleate and intermediate.Methods：The method was achieved on a Eclipse plus C18 column（3.0 mm×100 mm,1.8 μm） utilizing a mobile phase of 20 mmol·L-1 ammonium formate（A）-acetonitrile（B） with gradient elution（0-2 min,10%→50%B;2-4 min,50%→60%B;4-7 min,60%→90%B;7-8 min,90%B） at the flow rate of 1.0 mL·min-1.And the temperature of column was set at 50 ℃;The data was acquired in positive ion mode.Results： Standard curve was linear in the range of 0.20-5.01 μg·mL-1（r=0.9955）.The values of limit of quantification and limit of detection were 0.4 ng and 0.2 ng,respectively.RSDs for the intra-and inter-day were less than 6.7%.The recoveries（n=9） of ethyl p-toluenesulfonate in enalapril maleate and intermediate were 102.6% and 90.8%,respectively.Conclusion： The method is convenient and sensitive for detecting ethyl p-toluenesulfonate in enalapril maleate and intermediate.

关 键 词：高效液相色谱 四极杆-飞行时间质谱 马来酸依那普利 基因毒性杂质 对甲苯磺酸乙酯 杂质检测 中间体检测 安全监测 

分 类 号：R917[医药卫生—药物分析学]