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Development and validation of an efficient HPLC method for quantification of voriconazole in plasma and microdialysate reflecting an important target site

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Abstract

Voriconazole is a very potent antifungal agent used to treat serious fungal infections (candidiasis); it is also the therapy of choice for aspergillosis. After standard dosing, several factors affect exposure of voriconazole, resulting in large variability and demanding further elucidation of drug distribution. For measurements at the site of action, microdialysis is considered to be an outstanding minimally invasive method. For determination of voriconazole in microdialysate and human plasma a new, efficient, reliable, and robust HPLC assay using UV detection at 254 nm has been developed and validated. After simple sample preparation using acetonitrile for plasma and for microdialysate, 20 μL were injected and separated on an RP-18 column. The chromatographic run time was less than 4 min. Overall, the assay showed high precision (CV 93.9 to 99.5%) and accuracy (RE −96.7 to +107%) for both matrices. Of the 36 drug products typically co-administered with voriconazole, none except ambroxol interfered with its peak signal, and this interference was successfully managed. In summary, the method is highly suitable for application in (pre)clinical microdialysis studies, e.g., of critically ill patients with invasive mycoses.

Microdialysis probe situated in the interstitial space fluid containing voriconazole drug molecules (magenta coloured) extracting an important target site representative matrix (microdialysate) [Courtesy of CMA]

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Acknowledgements

The authors wish to thank Dorothea Frenzel and Lisanne Laetsch for their excellent contribution in conducting the experiments.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Institute of Pharmacy, Martin-Luther-Universitaet Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle, Germany

    Franziska Simmel, Alexander Zoerner & Charlotte Kloft

  2. Department of Anesthesia and Critical Care, Martin-Luther-Universitaet Halle-Wittenberg, 06120, Halle, Germany

    Jens Soukup & Joachim Radke

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  1. Franziska Simmel
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  2. Jens Soukup
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  3. Alexander Zoerner
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  4. Joachim Radke
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  5. Charlotte Kloft
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Correspondence to Charlotte Kloft.

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Simmel, F., Soukup, J., Zoerner, A. et al. Development and validation of an efficient HPLC method for quantification of voriconazole in plasma and microdialysate reflecting an important target site. Anal Bioanal Chem 392, 479–488 (2008). https://doi.org/10.1007/s00216-008-2286-3

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  • DOI: https://doi.org/10.1007/s00216-008-2286-3

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