HPLC-MS/MS法分离孟鲁司特顺式异构体及人血浆中孟鲁司特浓度的测定  

Development of an improved LC-MS/MS method for the determination of trans-montelukast in human plasma based on rapid separation of cis-and trans-montelukast

作　　者：谷雨[1] 关丽叶[1] 狄斌[1] 冉瑞雪[1] 蓝娟[1] 蒋孟虹[1] 马鹏程[2] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]中国医学科学院皮肤病研究所,南京210042

出　　处：《新疆医科大学学报》2013年第7期948-951,共4页Journal of Xinjiang Medical University

摘　　要：目的建立高效液相色谱-质谱联用方法实现孟鲁司特原形药物与其顺式异构体的快速分离,并测定人血浆中孟鲁司特原形药物的浓度。方法采用菲罗门Luna Phenyl-Hexyl(5μm,4.6×250mm)色谱柱;柱温25℃;流动相为乙腈-甲醇-水-甲酸(58∶20∶22∶0.2);流速为1.4mL/min-1;通过液相色谱串联质谱,电喷雾离子源(ESI+),以选择反应监测(SRM)方式进行检测;检测离子为孟鲁司特m/z 585.9[M+H]+→421.9[M+H]+,那格列奈(内标)m/z 318.1[M+H]+→166.0[M+H]+。结果孟鲁司特的最低定量限为1.846ng/mL,线性范围为1.846～1107.6ng/mL。结论该方法简便、灵敏度高,可以用来进行孟鲁司特人体药动学和生物等效性的研究。Objective A highly selective and specific LC-ESI-MS/MS method was developed and validated for the determination of trans-montelukast in human plasma based on the rapid separation of cis -and trans-montelukast. Methods Chromatographic separation of c/s-and trans-isomers was achieved with acetoni-trile-methanol-water-formic acid （58 ： 20 ： 22 ： 0.2, v/v） on a Luna Phenyl-Hexyl column with a total run time of 6.5 min. The detection was operated using a triple-quadrupole mass spectrometer in selective mul-tiple reaction monitoring （SRM） with the parent-to-product quantifier transitions [M＋ H]^＋ m/z 585.9→421.9 and [M＋H]^＋ m/z 318.1→166.0 for montelukast and nateglinide （IS）, respectively. Results The low limit of qualification was 1. 846 ng/mL with a standard correlation coefficient of 0. 9950. Conclusion This method is simple, sensitive, and suitable for clinical pharmacokinetics and bioequivalence studies.

关 键 词：孟鲁司特 顺式异构体 液相色谱-串联质谱 血浆 浓度测定 

分 类 号：R917[医药卫生—药物分析学]