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

Masatomo Takahashi, Yoshihiro Izumi, Fukumatsu Iwahashi, Yasumune Nakayama, Mitsuhiko Iwakoshi, Motonao Nakao, Seiji Yamato, Eiichiro Fukusaki, Takeshi Bamba

Research output: Contribution to journalArticle

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 13 C- or 2 H-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.

Original languageEnglish
Pages (from-to)9068-9076
Number of pages9
JournalAnalytical Chemistry
Volume90
Issue number15
DOIs
Publication statusPublished - Aug 7 2018

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Xenobiotics
Metabolites
2,4-Dichlorophenoxyacetic Acid
Isotopes
Labeling
Data mining
Metabolism
Liquid chromatography
Mass spectrometry
Cells

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry

Cite this

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. / Takahashi, Masatomo; Izumi, Yoshihiro; Iwahashi, Fukumatsu; Nakayama, Yasumune; Iwakoshi, Mitsuhiko; Nakao, Motonao; Yamato, Seiji; Fukusaki, Eiichiro; Bamba, Takeshi.

In: Analytical Chemistry, Vol. 90, No. 15, 07.08.2018, p. 9068-9076.

Research output: Contribution to journalArticle

Takahashi, Masatomo ; Izumi, Yoshihiro ; Iwahashi, Fukumatsu ; Nakayama, Yasumune ; Iwakoshi, Mitsuhiko ; Nakao, Motonao ; Yamato, Seiji ; Fukusaki, Eiichiro ; Bamba, Takeshi. / 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. In: Analytical Chemistry. 2018 ; Vol. 90, No. 15. pp. 9068-9076.
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