Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 44, Issue 5, Pages 1209-1213Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.44.5.1209-1213.2000
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A new selective high-performance liquid chromatography (HPLC) method with UV detection for the determination of the investigational triazole voriconazole in human plasma by using acetonitrile precipitation followed by reverse-phase HPLC on a C-18 column was compared with a simple agar well diffusion bioassay method with Candida kefyr ATCC 46764 as the assay organism. Pooled plasma was used to prepare standard and control samples for both methods. The results of analyses with spiked serum samples (run as unknowns) were concordant by the bioassay and HPLC methods, with expected values being obtained. HPLC demonstrated an improved precision (3.47 versus 12.12%) and accuracy (0.81 versus 1.28%) compared to those of the bioassay method. The range of linearity obtained by both methods (from 0.2 to 10 mu g/ml for HPLC and from 0.25 to 20 mu g/ml for the bioassay) includes the range of concentrations of voriconazole (from 1.2 to 4.7 mu g/ml) which are considered clinically relevant. Although either methodology could be used for the monitoring of patient therapy, the smaller variability observed with HPLC compared to that observed with the bioassay favors the use of HPLC for pharmacokinetic studies.
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