Cargando…

Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Aihua, Xu, Hui, Zhan, Ruoting, Chen, Weiwen, Liu, Jiawei, Chi, Yuguang, Chen, Daidi, Ji, Xiaoyu, Luo, Chaoquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154341/
https://www.ncbi.nlm.nih.gov/pubmed/28333075
http://dx.doi.org/10.3390/molecules22040489
_version_ 1783357678320353280
author Huang, Aihua
Xu, Hui
Zhan, Ruoting
Chen, Weiwen
Liu, Jiawei
Chi, Yuguang
Chen, Daidi
Ji, Xiaoyu
Luo, Chaoquan
author_facet Huang, Aihua
Xu, Hui
Zhan, Ruoting
Chen, Weiwen
Liu, Jiawei
Chi, Yuguang
Chen, Daidi
Ji, Xiaoyu
Luo, Chaoquan
author_sort Huang, Aihua
collection PubMed
description Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilot(TM) software. These predicted metabolites were further analyzed by MS(2) spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O-demethylation (M5-M7), didemethylation (M14–M16). The Phase II biotransformations include glucuronide conjugation (M8–M10) and sulfate conjugation (M11–M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O-demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids.
format Online
Article
Text
id pubmed-6154341
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61543412018-11-13 Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry Huang, Aihua Xu, Hui Zhan, Ruoting Chen, Weiwen Liu, Jiawei Chi, Yuguang Chen, Daidi Ji, Xiaoyu Luo, Chaoquan Molecules Article Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilot(TM) software. These predicted metabolites were further analyzed by MS(2) spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O-demethylation (M5-M7), didemethylation (M14–M16). The Phase II biotransformations include glucuronide conjugation (M8–M10) and sulfate conjugation (M11–M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O-demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids. MDPI 2017-03-23 /pmc/articles/PMC6154341/ /pubmed/28333075 http://dx.doi.org/10.3390/molecules22040489 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Aihua
Xu, Hui
Zhan, Ruoting
Chen, Weiwen
Liu, Jiawei
Chi, Yuguang
Chen, Daidi
Ji, Xiaoyu
Luo, Chaoquan
Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
title Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
title_full Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
title_fullStr Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
title_full_unstemmed Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
title_short Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
title_sort metabolic profile of skimmianine in rats determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154341/
https://www.ncbi.nlm.nih.gov/pubmed/28333075
http://dx.doi.org/10.3390/molecules22040489
work_keys_str_mv AT huangaihua metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT xuhui metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT zhanruoting metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT chenweiwen metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT liujiawei metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT chiyuguang metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT chendaidi metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT jixiaoyu metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry
AT luochaoquan metabolicprofileofskimmianineinratsdeterminedbyultraperformanceliquidchromatographycoupledwithquadrupoletimeofflighttandemmassspectrometry