Premium
Characterization of imatinib metabolites in rat and human liver microsomes: differentiation of hydroxylation from N ‐oxidation by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry
Author(s) -
Ma Shuguang,
Xu Yang,
Shou Magang
Publication year - 2009
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.4023
Subject(s) - chemistry , atmospheric pressure chemical ionization , metabolite , piperazine , chromatography , mass spectrometry , fragmentation (computing) , hydroxylation , chemical ionization , organic chemistry , ionization , ion , biochemistry , enzyme , computer science , operating system
Abstract In vitro metabolism of imatinib was investigated in rat and human liver microsomes. Atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) was applied in differentiating hydroxyl metabolites from N ‐oxides of imatinib because N ‐oxides are known to undergo deoxygenation during APCI. In addition, the major oxidative metabolite (M9, N ‐oxidation on the piperazine ring) was observed to undergo in‐source fragmentation by elimination of formaldehyde. This fragment ion resulted from Meisenheimer rearrangement with migration of the N ‐methyl group to the corresponding N ‐methoxyl piperazine, followed by elimination of formaldehyde due to thermal energy activation at the vaporizer of APCI source. The presence of this fragment ion distinguished not only N ‐oxide from isomeric hydroxylated metabolite, but also unambiguously indicated that oxidation occurred on the N ‐4 of the piperazine ring where the methyl group was attached. Copyright © 2009 John Wiley & Sons, Ltd.