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 journalArticlepeer-review

    23 Citations (Scopus)

    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.

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

    All Science Journal Classification (ASJC) codes

    • Analytical Chemistry

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