Loralie J Langman1, Felix Boakye-Agyeman. 1. Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Hilton 730, 200 First Street SW, Rochester, MN 55905, USA. Langman.loralie@mayo.edu
Abstract
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 micromol/L (0.1-20 microg/mL) shows good linearity (y=0.98x+0.36, r(2)=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 degrees 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.
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 micromol/L (0.1-20 microg/mL) shows good linearity (y=0.98x+0.36, r(2)=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 degrees 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.
Authors: Lorena Baietto; Antonio D'Avolio; Giusi Ventimiglia; Francesco Giuseppe De Rosa; Marco Siccardi; Marco Simiele; Mauro Sciandra; Giovanni Di Perri Journal: Antimicrob Agents Chemother Date: 2010-06-07 Impact factor: 5.191