Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 1033, Issue -, Pages 250-260Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2016.08.034
Keywords
Alantolactone; Intestinal bacteria biotransformation; UPLC-TOF-MS/MS; Multiple mass defect filter; Metabolites
Funding
- National Program on Key Basic Research Project of China (973 Program) [2012CB518601]
- Natural Science Foundation of Hebei Province [H2015206113]
- Project of Department of Education, Hebei Province [291090501]
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Alantolactone (AL), an active sesquiterpene originating from Inula helenium, is a potential anticancer and anti-inflammatory agent. However so far, studies on AL metabolism have not been reported. In the present study, we have investigated for the first time the in vivo and in vitro metabolites of AL using ultra performance liquid chromatography combined with time of flight mass spectrometry (UPLC-TOFMS/MS). A unique on-line information-dependent acquisition (IDA) method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was applied to trace all of the probable metabolites of AL. Five MMDF templates were set according to the core structure of AL and the general metabolite biotransformation patterns, and other five sulfur-containing dimer filter templates were first established on the basis of structural elucidation of AL metabolites obtained from rat intestinal bacteria biotransformation. As a result, 44 metabolites were characterized: 41 metabolites from rat urine, bile and feces after oral administration of AL, and 13 metabolites from AL biotransformation by rat intestinal bacteria. Particularly, 26 metabolites were identified as novel sulfur-containing products. The results indicated that addition of double bond at A(11,13) and oxidization were the main metabolic reactions of AL. A new metabolism pathway to produce addition products of H2S to AL and further generate a series of sulfur-containing dimers of AL was revealed. This study significantly enriched our knowledge about AL metabolism, which will lead to a better understanding of the safety and efficacy of AL. At the same time, the established methodology can be widely applied for the structural determination of the metabolites of other sesquiterpene containing alpha-methylene-gamma-lactone moiety. (C) 2016 Elsevier B.V. All rights reserved.
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