| RRC ID |
54371
|
| 著者 |
Takahashi M, Izumi Y, Iwahashi F, Nakayama Y, Iwakoshi M, Nakao M, Yamato S, Fukusaki E, Bamba T.
|
| タイトル |
Highly Accurate Detection and Identification Methodology of Xenobiotic Metabolites Using Stable Isotope Labeling, Data Mining Techniques, and Time-Dependent Profiling Based on LC/HRMS/MS.
|
| ジャーナル |
Anal Chem
|
| Abstract |
A generally applicable method to discover xenobiotic metabolites is important to safely and effectively develop xenobiotics. We propose an advanced method to detect and identify comprehensive xenobiotic metabolites using stable isotope labeling, liquid chromatography coupled with benchtop quadrupole Orbitrap high-resolution tandem mass spectrometry (LC/HRMS/MS), data mining techniques (alignment, peak picking, and paired-peaks filtering), in silico metabolism prediction, and time-dependent profiling. The LC/HRMS analysis was carried out using Arabidopsis T87 cultured cells treated with unlabeled or with 13C- or 2H-labeled 2,4-dichlorophenoxyacetic acid (2,4-D). Paired-peak filtering enabled the accurate detection of 83 candidates for 2,4-D metabolites without any false positive peaks derived from solvents or the biological matrix. We confirmed 10 previously reported 2,4-D metabolites and identified 16 novel 2,4-D metabolites. Our method provides accurate detection and identification of comprehensive xenobiotic metabolites and represents a potentially useful tool for elucidating xenobiotic metabolism.
|
| 巻・号 |
90(15)
|
| ページ |
9068-9076
|
| 公開日 |
2018-8-7
|
| DOI |
10.1021/acs.analchem.8b01388
|
| PMID |
30024726
|
| MeSH |
2,4-Dichlorophenoxyacetic Acid / metabolism*
Arabidopsis / cytology
Arabidopsis / drug effects
Arabidopsis / metabolism*
Cells, Cultured
Chromatography, High Pressure Liquid
Data Mining / methods
Herbicides / metabolism*
Isotope Labeling / methods
Tandem Mass Spectrometry / methods*
Xenobiotics / metabolism*
|
| IF |
6.785
|
| 引用数 |
1
|
| リソース情報 |
| シロイヌナズナ / 植物培養細胞・遺伝子 |
rpc00008 |
