Premium
Identification of metabolites of palmatine in rats after oral administration using ultra‐high‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry
Author(s) -
Wang Kun,
Chai Liwei,
Ding Liqin,
Qiu Feng
Publication year - 2017
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.7819
Subject(s) - chemistry , glucuronidation , chromatography , mass spectrometry , metabolite , metabolic pathway , hydroxylation , palmatine , sulfation , high performance liquid chromatography , demethylation , quadrupole time of flight , urine , metabolomics , tandem mass spectrometry , alkaloid , designer drug , metabolism , pharmacology , biochemistry , microsome , drug , gene expression , stereochemistry , dna methylation , gene , enzyme , medicine
Rationale Palmatine (PAL), a protopalmatine alkaloid, is an active constituent in a number of medicinal plants. In order to obtain a comprehensive and systematic metabolic profile of PAL, we investigated its metabolites in plasma, liver tissue, bile, urine, and feces samples after intragastrical administration to Sprague‐Dawley rats with a dose of 100 mg/kg/day. Methods In this study, a rapid and sensitive method by ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC/QTOF‐MS), and Metabolynx™ software with the mass defect filter (MDF) technique was developed for screening and identification of the metabolites. The structural elucidation of the metabolites was performed by comparing their molecular weights and fragment ions with those of the parent drug. Results As a result, a total of 58 metabolites were identified in rat biological samples including 46 metabolites in urine, 18 metabolites in plasma, 34 metabolites in bile, 26 metabolites in liver tissue, and 10 metabolites in feces. Among them, six major metabolites were fully confirmed using reference standards and others were identified by retention time, accurate mass and fragment ions. Conclusions These results indicated that phase I reactions (demethylation and hydroxylation) and phase II reaction (glucuronidation and sulfation) were the main metabolic pathways of PAL in vivo . This research enhances our understanding of metabolism of PAL in rats, and provides useful information on the action mechanism of PAL. Copyright © 2017 John Wiley & Sons, Ltd.