1. Detailed study of imatinib metabolization using high-resolution mass spectrometry
- Author
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Marcela Hrdá, Edgar Faber, Jitka Široká, Kateřina Mičová, Tomáš Adam, and David Friedecký
- Subjects
Resolution (mass spectrometry) ,Antineoplastic Agents ,Mass spectrometry ,Orbitrap ,Biochemistry ,Mass Spectrometry ,Analytical Chemistry ,law.invention ,Fragmentation (mass spectrometry) ,law ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Chromatography ,Plasma samples ,Chemistry ,Organic Chemistry ,Imatinib ,General Medicine ,Therapeutic monitoring ,Mass ,Molecular Weight ,Imatinib Mesylate ,Software ,medicine.drug ,Chromatography, Liquid - 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 5 ppm). 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 0.0001–1 μmol/L were identified by m/z values and confirmed by exact mass measurement of the MS2 and MS3 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.
- Published
- 2015