Background: Voriconazole (VOR), an antifungal agent, is clinically monitored to guide therapeutic dosing and avoid toxicity. It is believed that measurement of serum unbound VOR provides more accurate information, especially in hypoalbuminemia patients. We developed and validated an accurate, simple and fast test with ultrafiltration and ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) to measure unbound VOR in human serum.
Methods: The Agilent UPLC system coupled with a SCIEX QTRAP4000 MS with a positive ionization mode was developed and validated for VOR analysis.
Results: A good linearity was demonstrated from 0.02 to 2.5 μg/ml for unbound VOR (r2 = 0.9969). The within-run and between-run accuracy and precision was <5% and < 6%. The levels of total VOR were well correlated with reference laboratory results. Serum unbound VOR levels were correlated with the total VOR levels (r = 0.78, p < 0.0001). There was a reverse correlation between unbound VOR fractions and plasma albumin levels (p < 0.05). In hypoalbuminemia patients, the unbound VOR levels were increased to a higher degree than total VOR.
Conclusion: This assay is suitable for monitoring both unbound and bound VOR in cancer patients especially in those with hypoalbuminemia in clinical laboratories. Measurement of unbound VOR offers a better approach in prediction of VOR toxicity.
Keywords: Hypoalbuminemia; Therapeutic drug monitoring; UPLC-MS/MS; Ultrafiltration; Unbound voriconazole.
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