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Antimicrobial Agents and Chemotherapy, May 2000, p. 1209-1213, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Comparison of High-Performance Liquid Chromatographic and Microbiological Methods for Determination of Voriconazole Levels in Plasma

Sofia Perea,1,* Gennethel J. Pennick,1 Asha Modak,1 Annette W. Fothergill,1 Deanna A. Sutton,1 Daniel J. Sheehan,2 and Michael G. Rinaldi1,3

Department of Pathology, University of Texas Health Science Center at San Antonio,1 and Audie Murphy Division, South Texas Veterans Health Care System,3 San Antonio, Texas, and Pfizer Pharmaceutical Group, Pfizer Inc., New York, New York2

Received 2 August 1999/Returned for modification 7 November 1999/Accepted 28 January 2000

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 C18 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 µg/ml for HPLC and from 0.25 to 20 µg/ml for the bioassay) includes the range of concentrations of voriconazole (from 1.2 to 4.7 µg/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.

* Corresponding author. Department of Medicine/Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7881, San Antonio, TX 78229-3900. Phone: (210) 5671981. Fax: (210) 5673303. E-mail: Perea{at}UTHSCSA.EDU.

Antimicrobial Agents and Chemotherapy, May 2000, p. 1209-1213, Vol. 44, No. 5
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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