Measurement of voriconazole in serum and plasma

Objectives: Voriconazole is an antifungal agent structurally related to fluconazole. While regular drug monitoring is not indicated in most patients, it may help guide dosing in patients with reduced hepatic/renal function, on concurrent therapy with drugs that affect CYP2C9, with altered CYP2C9 genotypes, or during adverse drug reactions. Here we describe an HPLC method for determination of voriconazole. Methods: Samples, calibrators and controls were extracted using a liquid/liquid extraction. Chromatographic separation achieved using gradient solvent delivery with detection at 254 nm with a run time of 10 min. Concentration was calculated by comparison of peak height ratio of the drug with that of internal standard (IS) against a standard curve. Results: The assay is linear from 0.29 to 57 μmol/L (0.1–20 μg/mL) and shows good linearity (y = 0.98x + 0.36, r2 = 0.9978). The assay has inter- and intra-day precisions of < 10%. The stability of the drugs in specimens was tested for up to 7 days at room temperature, for 30 days frozen at − 20 °C, and through 3 freeze–thaw cycles and was found to be stable under those conditions. Conclusions: This describes a robust method for the determination of voriconazole in serum and plasma.