Determination and Clinical Application of Linezolid in Human Plasma by LC-MS/MS and HPLC
- VernacularTitle:LC-MS/MS及HPLC法检测利奈唑胺血药浓度及临床应用
- Author:
Haoqiang SHI
1
;
Juan HE
;
Jiaqian LU
;
Enqiang MAO
;
Zaiqian CHE
;
Bing CHEN
Author Information
1. 上海交通大学医学院附属瑞金医院药剂科 上海200025
- Keywords:
LC-MS/MS;
HPLC;
Linezolid;
Plasma concentration
- From:
China Pharmacist
2017;20(10):1718-1723
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To establish an LC-MS/MS and HPLC assay for the determination of linezolid in human plasma to be used for the therapeutic drug monitoring ( TDM) and pharmacokinetic study. Methods:Acetontrile containing furazolidone ( internal stand-ard) as the protein precipitation agent was added to100 μl human plasma, and then vibrated and centrifuged for the precipitation of plasma protein. ① The supernatant was eluted on an Eclipse XDB-C18 (100mm × 2. 1mm,3. 5μm) column with acetontrile and water (80 :20) as the mobile phase at the flow rate of 0. 3 ml·min-1. The electrospray ionization (ESI) source was applied and operated in the positive ion mode. The multiple reaction monitoring (MRM) modes with the transition of m/z338. 1→296. 2 (linezolid) and m/z226.1→122.0 (furazolidone) were used for the quantification. ② The supernatant was eluted on an Eclipse Eclipse XDB -C18(250 mm × 4. 6 mm, 5μm) column with acetontrile and 0. 1% formic acid (20 :80) as the mobile phase at the flow rate of 1. 0 ml·min-1 and detected at 254 nm. The established assays were used for the determination of linezolid in the plasma samples after the administra-tion. Results:Linezolid was linear within the range of 0. 05-30 μg·ml-1 for LC-MS/MS, and 0. 25-30 μg·ml-1 for HPLC ( r2 >0. 999). The extraction recovery and the matrix effect respectively was 82. 1%-91. 3% and 74. 0%-82. 3%. The relative recovery of LC-MS/MS and HPLC was 91. 2%-106. 4% and 100. 1%-111. 6%, respectively. The intra-and inter-day RSDs were both lower than 20%. There was a good correlation between LC-MS/MS and HPLC. The trough concentration of 12 patients was (1. 77 ± 1. 23) g· ml-1 and the plasma concentration of 5 patients 2h after linezolid adminstration was (13. 36 ± 2. 63) g·ml-1 , respectively. Conclu-sion:The established assays are simple, rapid, specific, sensitive and accurate, which are suitable for the TDM and pharmacokinetic study of linezolid.
