title: Simultaneous determination of the azoles voriconazole, posaconazole, isavuconazole, itraconazole and its metabolite hydroxy-itraconazole in human plasma by reversed phase ultra-performance liquid chromatography with ultraviolet detection.
abstract: A reversed phase ultra-performance liquid chromatography method was developed for the simultaneous quantitative determination of the systemically administered azoles voriconazole, posaconazole, isavuconazole, itraconazole and its metabolite hydroxy-itraconazole in plasma. The method involved a simple liquid-liquid extraction followed by ultra-performance liquid chromatography with an Acquity UPLC BEH Phenyl column and ultraviolet detection set at a wavelength of 260 nm. The assay was validated over the concentration range of 0.050-10,000 mg/l for all four azoles and one metabolite. The accuracies for the assay were 97-104%, inter- and intra-day coefficients of variation were <7.5% and extraction recoveries were 98% for voriconazole, posaconazole, isavuconazole and the internal standard (UK115794), and 79% and 88% for itraconazole and hydroxy-itraconazole respectively. This method proved to be simple, accurate, precise and fast and is currently in use in our laboratory for the quantitative analysis of these azoles for Therapeutic Drug Monitoring and pharmacokinetic research.
authors.affiliation: Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. C.Verweij@akf.umcn.nl
authors.forename: C P W G M Verweij-van
authors.initials: CP
authors.lastname: Wissen
authors.forename: D M
authors.initials: DM
authors.lastname: Burger
authors.forename: P E
authors.initials: PE
authors.lastname: Verweij
authors.forename: R E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: R J M
authors.initials: RJ
authors.lastname: Brüggemann
mesh_terms: D000935:Antifungal Agents / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D016903:Drug Monitoring; D004355:Drug Stability; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D014230:Triazoles / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles