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 mu g/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 mu g/mL. Conclusions We developed a simple and accurate method of drug monitoring, which could improve the efficacy and prevent adverse reactions of voriconazole.