Detailed study of imatinib metabolization using high-resolution mass spectrometry
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26199102
DOI
10.1016/j.chroma.2015.07.033
PII: S0021-9673(15)01001-8
Knihovny.cz E-resources
- Keywords
- Drug metabolization, Exact mass, Fragmentation, Orbital ion trap, Tyrosine kinase inhibitor,
- MeSH
- Chromatography, Liquid methods MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood drug therapy MeSH
- Mass Spectrometry methods MeSH
- Imatinib Mesylate blood therapeutic use MeSH
- Humans MeSH
- Molecular Weight MeSH
- Antineoplastic Agents blood therapeutic use MeSH
- Software MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Imatinib Mesylate MeSH
- Antineoplastic Agents MeSH
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.
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