title: Simultaneous determination of five systemic azoles in plasma by high-performance liquid chromatography with ultraviolet detection.
abstract: A simple, specific and automatable HPLC assay was developed for a simultaneous determination of systemic azoles (fluconazole, posaconazole, voriconazole, itraconazole and its metabolite hydroxyl-itraconazole, and ketoconazole) in plasma. The major advantage of this assay was sample preparation by a fully automatable solid phase extraction with Varian Plexa cartridges. C6-phenyl column was used for chromatographic separation, and UV detection was set at a wavelength of 260 nm. Linezolid was used as an internal standard. The assay was specific and linear over the concentration range of 0.05 to 40 microg/ml excepted for fluconazole which was between 0.05 and 100 microg/ml, and itraconazole between 0.1 and 40 microg/ml. Validation data for accuracy and precision for intra- and inter-day were good and satisfied FDA's guidance: CV between 0.24% and 11.66% and accuracy between 93.8% and 108.7% for all molecules. This assay was applied to therapeutic drug monitoring on patients hospitalized in intensive care and onco-hematologic units.
authors.affiliation: Clinical Pharmacokinetic Department, Victor Segalen Bordeaux 2 University and Clinical Pharmacy Haut-Lévêque Hospital, avenue de Magellan, 33604 Pessac, France. jean-baptiste.gordien@chu-bordeaux.fr
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Gordien
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pigneux
authors.forename: Stephane
authors.initials: S
authors.lastname: Vigouroux
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Accoceberry
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Bernadou
authors.forename: Audrey
authors.initials: A
authors.lastname: Rouault
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Saux
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D004355:Drug Stability; D015725:Fluconazole / Q000097:blood*; D006801:Humans; D017964:Itraconazole / Q000097:blood*; D007654:Ketoconazole / Q000097:blood*; D011743:Pyrimidines / Q000097:blood*; D011786:Quality Control; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013997:Time Factors; D014230:Triazoles / Q000097:blood*; D014466:Ultraviolet Rays; D065819:Voriconazole
chemical_list: D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D015725:Fluconazole; D065819:Voriconazole; D007654:Ketoconazole