Determination of polymyxin E in human plasma by LC-MS/MS and its application in therapeutic drug monitoring
10.16718/j.1009-7708.2025.02.006
- VernacularTitle: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
- Author:
Yan CHEN
1
;
Xiaolan HUANG
1
;
Yi LI
1
;
Xin LI
1
;
Beining GUO
1
;
Yaxin FAN
1
;
Hailan WU
1
;
Mengting CHEN
1
;
Wanzhen LI
1
;
Jing ZHANG
1
;
Xiaofen LIU
1
Author Information
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
- Publication Type:Journal Article
- Keywords:
polymyxin E;
liquid chromatography with tandem mass spectrometry;
therapeutic drug monitoring
- From:
Chinese Journal of Infection and Chemotherapy
2025;25(2):155-161
- CountryChina
- Language:Chinese
-
Abstract:
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,2.6 μm)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 0.031 2-6.24 mg/L and 0.006 15-1.23 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％-1 07.4％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.
