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Quantification of docetaxel and its main metabolites in human plasma by liquid chromatography/tandem mass spectrometry

Authors

  • J. Guitton,

    Corresponding author
    1. Laboratoire de ciblage thérapeutique en cancérologie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
    2. Laboratoire de Physiopathologie métabolique et rénale, Inserm U499, Faculté de Médecine Laennec, 8 rue G. Paradin, 69008 Lyon, France
    • Laboratoire de ciblage thérapeutique en cancérologie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France.
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  • S. Cohen,

    1. Fédération de Biochimie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
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  • B. Tranchand,

    1. Laboratoire de ciblage thérapeutique en oncologie, EA 3738, Faculté de Médecine Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
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  • B. Vignal,

    1. Fédération de Biochimie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
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  • J-P Droz,

    1. Service de cancérologie médicale, Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France
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  • M. Guillaumont,

    1. Fédération de Biochimie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
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  • M. Manchon,

    1. Fédération de Biochimie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
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  • G. Freyer

    1. Service de cancérologie médicale, Centre Léon Bérard, 28 rue Laënnec, 69008 Lyon, France
    2. Service d'oncologie médicale, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France
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Abstract

Docetaxel is an antineoplastic agent widely used in therapeutics. The objective of this study was to develop and validate a routine assay, using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), for the simultaneous quantification of docetaxel and its main hydroxylated metabolites in human plasma. A structural analogue, paclitaxel, was used as the internal standard. Determination of docetaxel and four metabolites (M1, M2, M3 and M4) was achieved using only 100 µL of plasma. Liquid-liquid extraction was used for sample preparation, with extraction efficiency of at least 90% for all analytes. Detection used positive-mode electrospray ionization in selected reaction monitoring mode. The lower limit of quantification (LLOQ) was 0.5 ng/mL for all analytes. The assay was linear in the calibration curve range 0.5–1000 ng/mL and acceptable precision and accuracy (<15%) were obtained with concentrations above the LLOQ. This method was sufficiently selective and sensitive for quantification of metabolites in plasma from cancer patients receiving docetaxel chemotherapy, and is suitable for routine analyses during pharmacokinetic studies. Copyright © 2005 John Wiley & Sons, Ltd.

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