title: Comparison and evaluation of a novel bioassay and high-performance liquid chromatography for the clinical measurement of serum voriconazole concentrations.
abstract: The aim of this study was to develop and validate a novel bioassay for determining serum voriconazole (VRC) concentrations and to compare its routine clinical performance with that of high-performance liquid chromatography (HPLC). The biological activity of VRC was measured by a plate diffusion assay using a VRC-hypersusceptible Candida kefyr strain. The bioassay's utility was tested by measuring steady-state VRC concentrations in 100 serum probes from VRC-treated patients. The HPLC system used solvent extraction with hexane:dichloromethane followed by reversed-phase HPLC with ultraviolet detection. The intra-day and inter-day accuracy of the bioassay was <5%, while that of HPLC was <1%. The precision (mean coefficient of variation, 3.5%) was equal for both the methods. The limit of quantification was lower for HPLC (0.2 mg l(-1)) than for the bioassay (0.5 mg l(-1)). The result of linear regression analysis was HPLC = 1.0178 (bioassay) + 0.328; R(2) = 0.88; n = 100. Results of the serum panel ranged from 0.5 to more than 8.0 mg l(-1) for the bioassay and from 0.26 to 10.1 mg l(-1) for HPLC. Especially in laboratories without access to HPLC, the bioassay may be a clinically useful tool for therapeutic drug monitoring.
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Dusiburg-Essen, Essen, Germany. joerg.steinmann@uk-essen.de
authors.forename: Joerg
authors.initials: J
authors.lastname: Steinmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Huelsewede
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Rath
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D001681:Biological Assay / Q000379:methods*; D002175:Candida / Q000187:drug effects; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044967:Serum / Q000737:chemistry*; D014230:Triazoles / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole