NDLI: Identification and characterization of in vitro phase I and reactive metabolites of masitinib using a LC-MS/MS method: bioactivation pathway elucidation

Content Provider	Royal Society of Chemistry (RSC)
Author	Amer, Sawsan M. Darwish, Hany W. Kadi, Adnan A. Attwa, Mohamed W.
Copyright Year	2017
Abstract	Masitinib is a selective tyrosine kinase inhibitor (TKI). It is currently registered in Europe for the treatment of mast cell tumors in dogs. The current study reports the identification and characterization of fourteen phase I metabolites of masitinib by reversed phase liquid chromatography triple quadrupole mass spectrometry (LC-QqQ-MS). Phase I metabolic reactions were reduction, demethylation, hydroxylation, oxidation and N-oxide formation. Structures of the proposed phase I metabolites showed high lability to form reactive metabolites. So incubation was performed in the presence of 1.0 mM GSH or 1.0 mM KCN to check for reactive metabolites. No GSH adduct was found, while eight cyano adduct structures were determined based on full MS scan and MS2 scan data for each metabolite. Interestingly, a literature review showed no previous studies have been made on the in vitro metabolism of masitinib or detailed structural identification of the formed metabolites.
Starting Page	4479
Ending Page	4491
Page Count	13
File Format	HTM / HTML PDF
ISSN	20462069
Volume Number	7
Issue Number	8
Journal	RSC Advances
DOI	10.1039/c6ra25767d
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Hydroxylation Metabolite Europe High-performance liquid chromatography Tyrosine-kinase inhibitor Quadrupole mass analyzer Demethylation Drug metabolism Mast cell Amine oxide Masitinib Mass spectrometry Adduct
Content Type	Text
Resource Type	Article
Subject	Chemistry Chemical Engineering

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