液相色谱串联质谱法测定人血浆中多黏菌素E浓度及其在治疗药物监测中的应用  

Determination of polymyxin E in human plasma by LC-MS/MS and its application in therapeutic drug monitoring

作　　者：陈焰 黄晓岚 李熠 李鑫 郭蓓宁 范亚新 毋海兰 陈梦婷 李婉贞 张菁 刘笑芬 CHEN Yan;HUANG Xiaolan;LI Yi;LI Xin;GUO Beining;FAN Yaxin;WU Hailan;CHEN Mengting;LI Wanzhen;ZHANG Jing;LIU Xiaofen(Institute of Antibiotics,Huashan Hospital,Fudan University,Key Laboratory of Clinical Pharmacology of Antibiotics,Ministry of Health,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院抗生素研究所,国家卫生健康委员会抗生素临床药理重点实验室,上海200040

出　　处：《中国感染与化疗杂志》2025年第2期155-161,共7页Chinese Journal of Infection and Chemotherapy

基　　金：上海申康医院发展中心市级医院新兴前沿技术联合攻关项目(SHDC12020106);上海市科学技术委员会项目(19411964900);上海市领军人才(LJ2016-01)。

摘　　要：目的建立一种高效、简便的测定人血浆中多黏菌素E的液相色谱串联质谱法(LC-MS/MS),为多黏菌素E治疗药物监测提供支持。方法采用AB SCIEX HPLC-4500MD液质联用仪测定,色谱条件采用0.2%甲酸水和0.2%甲酸乙腈梯度洗脱,色谱柱为Phenomenex Kinetex XB-C18柱(100 mm×2.1 mm,2.6μm),质谱采用正离子多反应监测检出模式,待测物多黏菌素E1、E2和内标多黏菌素B1的离子对分别为m/z 390.7→101.3、m/z 386.0→101.2、m/z 402.3→101.2。血浆样本采用蛋白沉淀进行预处理。结果多黏菌素E1、E2分别在0.0312~6.24 mg/L、0.00615~1.23 mg/L范围内呈良好的线性,在血浆中的批内准确度、精密度分别为89.4%~99.8%、4.9%~8.9%和91.5%~108.2%、2.8%~8.5%,批间准确度、精密度分别为91.8%~104.7%、4.1%~7.6%和95.6%~105.2%、4.2%~9.8%。在6个不同来源空白血浆中,多黏菌素E1、E2的平均内标归一化基质效应因子分别为96.9%~111.2%、106.1%~112.8%,在脂血血浆中分别为102.5%~106.8%、98.8%~105.2%,在溶血血浆中分别为107.8%~108.9%、106.9%~107.4%,精密度均小于15.0%。多黏菌素E1、E2的平均提取回收率在102.9%~107.5%范围内,内标多黏菌素B1平均回收率为107.0%,精密度<3.7%。结论该研究成功建立一种简单、高效的测定人血浆中多黏菌素E1和E2的LC-MS/MS方法,可用于多黏菌素E治疗药物浓度监测及药代动力学研究。Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2%formic acid in water and 0.2%formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm×2.1 mm,2.6μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.0312-6.24 mg/L and 0.00615-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4%to 99.8%and 91.5%to 108.2%,respectively,while the between-run accuracy ranged from 91.8%to 104.7%and 95.6%to 105.2%,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9%to 8.9%and 2.8%to 8.5%,respectively,while the between-run precision ranged from 4.1%to 7.6%and 4.2%to 9.8%,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9%-111.2%and 106.1%-112.8%in blank plasma samples from 6 different sources,102.5%-106.8%and 98.8%-105.2%in lipemic plasma,respectively,107.8%-108.9%and 106.9%-107.4%in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0%.The average recovery rate was 102.9%-107.5%for polymyxin E1 and E2,and 107.0%for internal standard polymyxin B1.The precision was less than 3.7%.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E

关 键 词：多黏菌素E 液相色谱串联质谱法 治疗药物监测 

分 类 号：R978.16[医药卫生—药品]