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Simultaneous Quantification of Voriconazole and Its N-Oxide Metabolite in Human Plasma by an Easy and Rapid Isocratic LC Method with UV Detection

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Abstract

We present a simple and reliable method for simultaneous determination of voriconazole and its main metabolite resulting from N-oxidation (UK-121,265), in human plasma. The work-up procedure used acetonitrile and potassium salts to precipitate plasma proteins. No internal standard was used. The chromatographic system used a LiChroCART® 250-4 cartridge packed with LiChrospher® 100 RP-8 (diameter particules, 5 μm). The UV monochromatic detector was set on 260 nm. The mobile phase consisted of a 60/40 (v/v) mixture of acetonitrile and water. The flow rate was 1 mL min−1. The retention times for voriconazole and its metabolite were 8.98 and 4.02 min respectively, and total run time was 12 min. The linearity of the method was investigated from 0.31 to 10.0 mg L−1; the lowest limit of quantification was 0.30 mg L−1. Precision ranged from 2.41% to 6.32% for voriconazole and 0.80% to 11.6% for the N-oxide voriconazole metabolite. Accuracy was between 93.0% and 101% for voriconazole and 90.0% and 101% for the N-oxide voriconazole metabolite. This rapid and accurate method could be interesting to investigate metabolite/voriconazole ratio with respect to CYP2C19 genetic status and CYP3A4 activity changes.

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Authors and Affiliations

  1. Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, CHU Montpellier, University Montpellier 1, France

    Céline Eiden, Olivier Mathieu, Hélène Peyrière, Dominique Hillaire-Buys & Marylène Cociglio

Authors
  1. Céline Eiden
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  2. Olivier Mathieu
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  3. Hélène Peyrière
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  4. Dominique Hillaire-Buys
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  5. Marylène Cociglio
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Correspondence to Hélène Peyrière.

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Eiden, C., Mathieu, O., Peyrière, H. et al. Simultaneous Quantification of Voriconazole and Its N-Oxide Metabolite in Human Plasma by an Easy and Rapid Isocratic LC Method with UV Detection. Chroma 67, 275–280 (2008). https://doi.org/10.1365/s10337-007-0508-z

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  • DOI: https://doi.org/10.1365/s10337-007-0508-z

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