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论文类型：期刊论文

发表时间：2018-10-01

发表刊物：JOURNAL OF CHROMATOGRAPHIC SCIENCE

收录刊物：SCIE、PubMed

卷号：56

期号：9

页面范围：828-834

ISSN号：0021-9665

摘要：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 <9.67% and 13.0%, and the precisions were <14.5% at all tested concentrations. The entire analysis time for the four drugs was only 5 min for each sample. The currently developed assay was successfully applied for the therapeutic drug monitoring of 85 patients administered with standard drug treatments, demonstrating its high-throughput clinical usage for the therapeutic drug monitoring.