Fast and simple LC-MS/MS method for quantifying plasma voriconazole

Background: An increasing number of publications point to the importance of voriconazole plasma monitoring. Our aim was to develop a fast and simple LC-MS/MS method for the quantification of plasma voriconazole. Methods: 20 mu L of plasma was extracted by adding a precipitation reagent containing the internal standard (d(3)-voriconazole). Analysis was performed on a Quattro Micro tandem mass spectrometer equipped with an Alliance HPLC 2795 separations module. MRM transitions were m/z 350.0 -> 281.4 for voriconazole and m/z 353.0 -> 284.4 for d(3)-voriconazole. Quantification was done by both linear calibration curves and multiplication of the response ratio by a predefined factor. Results: A method using protein precipitation as only pretreatment with an analysis time of 2 min was developed. Within- and between-run precision, expressed as coefficient of variation, at 6 concentrations ranged from 2.8% to 11.7%. Accuracy, expressed as a percentage of the theoretically added concentration, ranged from 89.0% to 109.0%. Linearity was demonstrated from 0.06 mg/L (0.17 mu M) to 20.0 mg/L (57.3 mu M). Conclusions: The described method offers a simple and rapid analysis of voriconazole in human plasma for clinical routine. Quantification with a predefined factor permits omitting calibration to each run and thereby reduces workload, costs and turn-around time. (C) 2012 Elsevier B.V. All rights reserved.