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OBJECTIVES: This study aims to present a strategy to optimize a liquid chromatography
coupled to tandem mass spectrometry (LC-MS/MS) method for voriconazole and voriconazole-N-oxide
with an stable isotopically labelled internal standard. METHODS: Protein precipitation
was used as extraction method and detection was carried out with LC-MS/MS using 13C2-2H3-voriconazole
as internal standard. RESULTS: Voriconazole and voriconazole-N-oxide concentrations
can be detected with good accuracy and reproducibility within the therapeutic range
(ref. 1-6 mg/L). Accuracy ranged from -3.0%-4.2% for voriconazole and -1.0%-3.8% for
voriconazole-N-oxide and overall coefficients of variation (CV) ranged from 2.9%-7.5%
for voriconazole and 4.0%-10.8% for voriconazole-N-oxide. However, voriconazole-N-oxide
is relatively unstable at room temperature (Low QC sample: -81.1% after 120 hours),
therefore samples should be cooled (2-8°C) after sampling to detect reliable voriconazole-N-oxide
concentrations. CONCLUSIONS: An accurate and simple assay for the analysis of voriconazole
and voriconazole-N-oxide to enable therapeutic drug monitoring was developed and validated
for all critical parameters.