A LC-MS-MS assay for simultaneous determination of two glycopeptides and two small molecule compounds in human plasma

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 μL 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 × 50 mm, 2.7 μm). 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 μg/mL for meropenem; 1-100 μg/mL for teicoplanin and vancomycin; 0.3-10 μg/mL for voriconazole. The lower limit of quantitation (LLOQ) of meropenem and voriconazole were 0.30 μg/mL; and the LLOQ of teicoplanin and vancomycin were 1.0 μg/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.