title: Quantification of docetaxel and its main metabolites in human plasma by liquid chromatography/tandem mass spectrometry.
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 microL 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.
authors.affiliation: Laboratoire de ciblage thérapeutique en cancérologie, Centre Hospitalier Lyon-Sud, 165 chemin du grand Revoyet, 69495 Pierre Bénite Cedex, France. Jerome.Guitton@chu-lyon.fr
authors.forename: J
authors.initials: J
authors.lastname: Guitton
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: B
authors.initials: B
authors.lastname: Tranchand
authors.forename: B
authors.initials: B
authors.lastname: Vignal
authors.forename: J-P
authors.initials: JP
authors.lastname: Droz
authors.forename: M
authors.initials: M
authors.lastname: Guillaumont
authors.forename: M
authors.initials: M
authors.lastname: Manchon
authors.forename: G
authors.initials: G
authors.lastname: Freyer
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*; D002138:Calibration; D002853:Chromatography, Liquid; D000077143:Docetaxel; D006801:Humans; D007275:Injections, Intravenous; D015394:Molecular Structure; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel