A LC-MS-MS assay for simultaneous determination of two glycopeptides and two small molecule compounds in human plasma
A LC-MS-MS assay for simultaneous determination of two glycopeptides and two small molecule compounds in human plasma
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LC→MS-MS 测定同时测定人血浆中的两种糖肽和两种小分子化合物
DOI：
10.1093/chromsci/bmy060
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发表时间：
2018-10-01
影响因子：
1.3
通讯作者：
Li, Yanyan
中科院分区：
文献类型：
--
作者：
Shi, Meiyun;Zhao, Xiaojun;Li, Yanyan
在本研究中，开发并验证了一种新型高通量液相色谱-串联质谱（LC-MS-MS）测定法，用于同时测定人血浆中的两种糖肽（万古霉素、替考拉宁）和两种小分子化合物（美罗培南、伏立康唑）。仅使用50 μ L人血浆以临床浓度水平同时定量这四种药物。在相对简单的蛋白质沉淀后，然后用移动的流动相乙腈：0.1%甲酸（5：95，v/v）稀释上清液，以避免溶剂效应并降低基质效应。然后，在Agilent Zorbax SB-C18柱（4.6 × 50 mm，2.7 μ m）上分离目标化合物。所有目标化合物均采用正离子模式检测。替考拉宁浓度测定为6种组分（A2-1、A2-2、A2-3、A2-4、A2-5和A3-1）的总和。该方法在美罗培南浓度范围0.3-30 μ g/mL、替考拉宁和万古霉素浓度范围1-100 μ g/mL、伏立康唑浓度范围0.3-10 μ g/mL内呈线性。美罗培南和伏立康唑的定量下限（LLOQ）为0.30 μ g/mL;替考拉宁和万古霉素的LLOQ为1.0 μ g/mL。日内和日间准确度为
In this study, a novel and high-throughput liquid chromatography-tandem mass spectrometric (LC-MS-MS) assay was developed and validated for simultaneous determination of two glycopeptides (vancomycin, teicoplanin) and two small molecule compounds (meropenem, voriconazole) in human plasma. Only 50 mu L of human plasma is used to quantify these four drugs simultaneously at clinical concentration levels. After a relative simple protein precipitation, the supernatant was then diluted with mobile phase acetonitrile: 0.1% formic acid (5:95, v/v) to avoid solvent effect and reduce the matrix effect. Then, the target compounds were separated on an Agilent Zorbax SB-C18 column (4.6 x 50 mm, 2.7 mu m). All the target compounds were detected by positive ion mode. The teicoplanin concentration was determined as the sum of six components (A2-1, A2-2, A2-3, A2-4, A2-5 and A3-1). The method was linear in the concentration range 0.3-30 mu g/mL for meropenem; 1-100 mu g/mL for teicoplanin and vancomycin; 0.3-10 mu g/mL for voriconazole. The lower limit of quantitation (LLOQ) of meropenem and voriconazole were 0.30 mu g/mL; and the LLOQ of teicoplanin and vancomycin were 1.0 mu g/mL. The intra- and inter-day accuracies were