Determination of voriconazole in human plasma by liquid chromatography-tandem mass spectrometry and its application in therapeutic drug monitoring in Chinese patients

OBJECTIVE: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of voriconazole in human plasma, and to evaluate its application in clinical therapeutic drug monitoring. METHOD: Plasma samples were obtained from Chinese patients receiving voriconazole, precipitated with methanol (using fluconazole as an internal standard), and then subjected to LC-MS/MS using an SB C(18) column with a methanol and water mobile phase at a flow rate of 0.4 mL/minute. Quantification was performed by multiple-reaction monitoring using the precursor and product ion pair m/z 350–280.9 for voriconazole and m/z 307–219.9 for fluconazole. RESULTS: The calibration curve was linear over a range of 0.1–10.0 µg/mL (R(2) = 0.9995). The inter-day and intra-day relative standard deviations were <7.68% and <8.97%, respectively. Extraction recovery, matrix effect, and stability were also validated. Sixty-eight plasma samples from 42 patients were analyzed, and the voriconazole concentrations in 25 samples (36.8%) were outside the optimal range of 1.5–4.5 µg/mL. CONCLUSIONS: We developed a simple and accurate method of drug monitoring, which could improve the efficacy and prevent adverse reactions of voriconazole.