Simultaneous Quantification of Vancomycin, Linezolid and Voriconazole in Human Plasma by UHPLC–MS/MS: Application in Therapeutic Drug Monitoring

Abstract

Objective: Individual differences challenge the treatment of vancomycin, linezolid and voriconazole in severe infections. This study aimed to build a simple and economical method for simultaneous determination of the three antibiotics in human plasma by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) and provided a reference for therapeutic drug monitoring (TDM) of infected patients. Methods: The plasma samples were precipitated by acetonitrile and detected and separated on a shim-pack GIST C18 column following the gradient elution within 5 min. Mass quantification was performed on multiple reaction monitoring mode under positive electrospray ionization. Results: The linear ranges of vancomycin, linezolid and voriconazole were 1.00–100.00, 0.10–15.00 and 0.10–20.00 μg·mL−1, respectively, with good linearity (R2 >0.99). The accuracy and precision, matrix effect, extraction recovery and stability were validated, and the results all meet the acceptance criteria of China Food and Drug Administration (CFDA) guidelines. Conclusion: The UHPLC–MS/MS method was established and validated for the simultaneous determination of vancomycin, linezolid and voriconazole in human plasma and successfully applied to routine TDM for individualized treatment.