Abstract
A simple, sensitive and rapid high-performance liquid chromatographic (HPLC) method for the determination of voriconazole in human serum or plasma was developed. Voriconazole and internal standard clonazepam were extracted from plasma or serum with methanol and analyzed on a Microsorb-MV C18 column with ultraviolet (UV) detection set at wavelengths of 256 and 310 nm, respectively. The calibration curve was linear through the range of 0.1-10 mg/L using a 0.1 mL sample volume. The within-run and between-run precisions were all less than 6%. Accuracies ranged from 97 to 106%. Absolute recovery was 96.4 ± 1.3% for voriconazole. The method has been applied to monitor voriconazole use in order to ascertain clinical efficacy and minimize toxic effects.
Highlights
Voriconazole is a broad-spectrum, second-generation triazole antifungal agent, designated chemically as (2R, 3S)-2-(2,4difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)2-butanol, that is a derivative of fluconazole
The methanol extracts produced shaper peaks of voriconazole and clonazepam which translated into higher peakheights for both compounds
Methanol was chosen as the precipitation solvent, and the recoveries of clonazepam and voriconazole were 93.1 ± 0.7% and 96.4 ± 1.2%, respectively
Summary
Voriconazole is a broad-spectrum, second-generation triazole antifungal agent, designated chemically as (2R, 3S)-2-(2,4difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1-yl)2-butanol, that is a derivative of fluconazole. Voriconazole has been widely used for the treatment of invasive fungal diseases, invasive aspergillosis. Voriconazole is approved for the treatment of invasive candidosis, as well as for less frequent fungal infections such as fusariosis and scedosporiosis. Its fungicidal action is due to inhibition of fungal cytochrome P450-dependent 14α-sterol demethylase, a key enzyme of ergosterol biosynthesis. Inhibition of ergosterol biosynthetic pathway leads to a disruption of the integrity and the function of the fungal membrane. Voriconazole serum concentrations were varied and unpredictable [2]. High variability had been observed in serum voriconazole concentration within and between individuals [3-5]. Serum voriconazole concentration is unpredictable, therapeutic drug monitoring (TDM) could be most useful in order to ascertain clinical efficacy and to minimize toxic effects
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