Detailed study of imatinib metabolization using high-resolution mass spectrometry
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26199102
DOI
10.1016/j.chroma.2015.07.033
PII: S0021-9673(15)01001-8
Knihovny.cz E-zdroje
- Klíčová slova
- Drug metabolization, Exact mass, Fragmentation, Orbital ion trap, Tyrosine kinase inhibitor,
- MeSH
- chromatografie kapalinová metody MeSH
- chronická myeloidní leukemie krev farmakoterapie MeSH
- hmotnostní spektrometrie metody MeSH
- imatinib mesylát krev terapeutické užití MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- protinádorové látky krev terapeutické užití MeSH
- software MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imatinib mesylát MeSH
- protinádorové látky 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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