Characterization of in vivo metabolites in rat urine following an oral dose of masitinib by liquid chromatography tandem mass spectrometry

Chemistry Central Journal
Adnan A KadiMohamed W Attwa

Abstract

Masitinib (MST) is an orally administered drug that targets mast cells and macrophages, important cells for immunity, by inhibiting a limited number of tyrosine kinases. It is currently registered in Europe and USA for the treatment of mast cell tumors in dogs. AB Science announced that the European Medicines Agency has accepted a conditional marketing authorization application for MST to treat amyotrophic lateral sclerosis. In our work, we focused on studying in vivo metabolism of MST in Sprague-Dawley rats. Single oral dose of MST (33 mg kg-1) was given to Sprague-Dawley rats (kept in metabolic cages) using oral gavage. Urine was collected and filtered at 0, 6, 12, 18, 24, 48, 72 and 96 h from MST dosing. An equal amount of ACN was added to urine samples. Both organic and aqueous layers were injected into liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect in vivo phase I and phase II MST metabolites. The current work reports the identification and characterization of twenty in vivo phase I and four in vivo phase II metabolites of MST by LC-MS/MS. Phase I metabolic pathways were reduction, demethylation, hydroxylation, oxidative deamination, oxidation and N-oxide formation. Phase II metabolic pathways were the...Continue Reading

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Citations

Mar 25, 2019·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Sonali JainPinaki Sengupta
Jul 22, 2018·Journal of Translational Medicine·Long ZhengDong Zhu
Dec 7, 2020·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Mokhtar M MabroukSamah F El-Malla

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Methods Mentioned

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