Imatinib metabolite profiling in parallel to imatinib quantification in plasma of treated patients using liquid chromatography-mass spectrometry.

Détails

ID Serval
serval:BIB_9FBD3ADEE3DF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Imatinib metabolite profiling in parallel to imatinib quantification in plasma of treated patients using liquid chromatography-mass spectrometry.
Périodique
Journal of mass spectrometry
Auteur(s)
Rochat B., Fayet A., Widmer N., Lahrichi S.L., Pesse B., Décosterd L.A., Biollaz J.
ISSN
1076-5174
Statut éditorial
Publié
Date de publication
02/2008
Peer-reviewed
Oui
Volume
43
Numéro
6
Pages
736-52
Langue
anglais
Notes
Publication types: Journal Article - Publication Status: ppublish
Résumé
Besides affecting the systemic bioavailability of the parent drug, drug metabolizing enzymes (DMEs) may produce bioactive and/or toxic metabolites of clinical interest. We have investigated the capability to analyze simultaneously the parent drug and newly identified metabolites in patients' plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The anticancer drug, imatinib, was chosen as a model drug because it has opened a new area in cancer therapy and is given orally and chronically. In addition, resistance and rare but sometimes severe side effects have been reported with this therapy. The quantification of imatinib and the profiling of its metabolites in plasma were established following three steps: (1) set-up of a generic sample extraction and LC-MS/MS conditions, (2) metabolite identification by LC-MS/MS using either in vitro incubations performed with human liver microsomes (HLMs) or patient plasma samples, (3) the simultaneous determination of plasma levels of imatinib and 14 metabolites in the plasma samples of 38 patients. Partial or cross method validation has been done and revealed that precise determinations of metabolite levels can be performed whereas pure standards are not available. Preliminary results indicate that the disposition of imatinib and its metabolites is related to interindividual variables and that outlier metabolite profiles can be revealed. This article underscores that, in addition to usual therapeutic drug monitoring (TDM), LC-MS/MS methods can simultaneously record a complete drug metabolic profile enabling various correlation studies of clinical interest.
Mots-clé
Antineoplastic Agents, Chromatography, Liquid, Humans, Leukemia, Piperazines, Pyrimidines, Tandem Mass Spectrometry
Pubmed
Web of science
Création de la notice
05/03/2008 16:31
Dernière modification de la notice
03/03/2018 20:03
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