title: Detailed study of imatinib metabolization using high-resolution mass spectrometry.
abstract: Modern high resolution mass spectrometry offers unique identification capability in drug metabolism studies. In this work detailed imatinib metabolization in the plasma of patients with chronic myeloid leukemia is presented. The metabolites were separated by liquid chromatography on a C18 column with mass spectrometry detection via an Orbitrap Elite instrument (Thermo Scientific) based on exact mass measurement. A scan range of m/z 350-1200 resolution of 60,000 was applied (mass accuracy of 5ppm). The data were evaluated using the advanced software for mass spectrometry Mass Frontier and MetWorks. In all plasma samples, studied 90 metabolites in the concentration range of 0.0001-1μmol/L were identified by m/z values and confirmed by exact mass measurement of the MS(2) and MS(3) fragmentations. In order to achieve optimal clinical response and avoid toxicity, current therapeutic monitoring of parent drug is a useful tool for the individualization of treatment. Current high-resolution mass spectrometry possesses the potential to broaden this approach by monitoring number of potentially clinically relevant drug metabolites.
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Czech Republic; Laboratory for Inherited Metabolic Disorders, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Czech Republic. Electronic address: david.friedecky@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Friedecký
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Czech Republic; Laboratory for Inherited Metabolic Disorders, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Mičová
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Czech Republic.
authors.forename: Edgar
authors.initials: E
authors.lastname: Faber
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Hrdá
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Široká
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, Czech Republic; Laboratory for Inherited Metabolic Disorders, Faculty of Medicine and Dentistry, Palacky University in Olomouc, University Hospital Olomouc, Czech Republic; Department of Clinical Chemistry, University Hospital Olomouc, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Adam
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000627:therapeutic use; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D000068877:Imatinib Mesylate / Q000097:blood* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy; D013058:Mass Spectrometry / Q000379:methods; D008970:Molecular Weight; D012984:Software
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate
keywords: Drug metabolization; Exact mass; Fragmentation; Orbital ion trap; Tyrosine kinase inhibitor