Comparison of LC-MS(3) and LC-MRM Method for Quantifying Voriconazole and Its Application in Therapeutic Drug Monitoring of Human Plasma

The TDM of voriconazole which exhibits wide inter-individual variability is indispensable for treatment in clinic. In this study, a method that high-performance liquid chromatography tandem mass spectrometry cubed (HPLC-MS(3)) is first built and validated to quantify voriconazole in human plasma. The system is composed of Shimadzu Exion LC(TM) UPLC coupled with a Qtrap 5500 mass spectrometer. The separation of voriconazole is performed on a Poroshell 120 SB-C18 column at a flow rate of 0.8 mL/min remaining 7 min for each sample. The calibration curves are linear in the concentration range of 0.25–20 μg/mL. Intra-day and inter-day accuracies and precisions are within 8.0% at three concentrations, and the recoveries and matrix effect are all within accepted limits. In terms of stability, there is no significant degradation of voriconazole under various conditions. The HPLC-MS(3) and HPLC-MRM (multiple reaction monitoring) methods are compared in 42 patients with Passing–Bablok regression and Bland–Altman plots, and the results show no significant difference between the two methods. However, HPLC-MS(3) has a higher S/N (signal-to-noise ratio) and response than the MRM. Finally, the HPLC-MS(3) assay is successfully applied to monitor the TDM (therapeutic drug monitoring) of voriconazole in human plasma, and this verifies that the dosing guidelines for voriconazole have been well implemented in the clinic and patients have received excellent treatment.