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

Abstract

BACKGROUND 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. METHODS 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. RESULTS 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 and LC-MS/MS, revealed mean biases of 11% and 4%, respectively. CONCLUSIONS We have developed an accurate, rapid, and sensitive LC-MS/MS assay for quantification of human serum voriconazole. Our assay reduces current specimen volume requirements, decreases result turnaround time, and saves institutional funds.

DOI: 10.1016/j.jchromb.2015.02.011

Cite this paper

@article{Mak2015DevelopmentAV, title={Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to quantify serum voriconazole.}, author={Justin Mak and Kirk K Sujishi and Deborah L. French}, journal={Journal of chromatography. B, Analytical technologies in the biomedical and life sciences}, year={2015}, volume={986-987}, pages={94-9} }