Ixerin Z, one of major sesquiterpene lactones from Ixeris sonchifolia Hance, was considered to be a major active compound because of their special structure and activity. However, studies on Ixerin Z metabolism have rarely been reported. This study is the first to investigate the in vivo metabolism of Ixerin Z following intravenously administered of Ixerin Z by HPLC-LTQ-Orbitrap mass spectrometry and multiple mass defect filters (MMDF) technique. A total of 41 metabolites as well as parent drug after using two MMDF filter templates were unambiguously or tentatively identified based on accurate mass measurements, fragmentation patterns, and chromatographic retention times. The metabolic pathways of Ixerin Z were also proposed for the first time. The results demonstrated that Ixerin Z underwent extensive metabolic reaction including hydrogenation, hydroxylation, hydrolysis, methylation, cysteine conjugation, glutathione (GSH) conjugation, sulfate conjugation, N-acetylcysteine conjugation, and glucuronidation. In conclusion, our study provided an insight into the metabolism of Ixerin Z.
Keywords: HPLC–LTQ-Orbitrap; Ixerin Z; Ixeris sonchifolia Hance; Metabolites; Multiple mass defect filter.
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