Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify serum voriconazole

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Justin MakDeborah French

Abstract

Voriconazole is an azole antifungal drug indicated for use in the treatment of invasive aspergillosis. Due to the large intra- and interindividual variation seen in voriconazole pharmacokinetics along with a high probability of drug-drug interactions, therapeutic drug monitoring is of considerable clinical value. As such, we developed and validated a LC-MS/MS assay to quantify serum voriconazole to improve turnaround time and decrease costs. After protein precipitation with D3-voriconazole (deuterated internal standard) in acetonitrile was performed, samples were separated by gradient elution and injected into the mass spectrometer with a total run-time of 4 min per sample. Multiple reaction monitoring was employed using Q1/Q3 transitions of 350/127 and 350/281 for voriconazole and 353/284 and 353/127 for D3-voriconazole. Sample preparation took 30 min for 6 patient samples. The limit of quantitation was 0.1 μg/mL and the linearity ranged from 0.1 μg/mL to 10.0 μg/mL. Extraction recovery was ∼69% and ion suppression ∼13%. Intra- and inter-assay imprecision (%CV) was <5% at the limit of quantitation and <4% through the rest of the linear range. Method comparisons between our assay and two reference laboratory methods, HPLC-UV an...Continue Reading

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Citations

Aug 5, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Cristina CampestreSimone Carradori
Jan 12, 2020·Clinical Chemistry and Laboratory Medicine : CCLM·Christine L SkaggsLindsey M Kirkpatrick

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