{
  "abstract": "Stable isotope-resolved metabolomics (SIRM) using dual-isotope tracers, such as [U-13C5,15N2]glutamine, provides complementary insight into carbon and nitrogen metabolism and their integration across interconnected metabolic pathways. However, distinguishing closely spaced 13C- and 15N-containing isotopologues requires resolving power that conventional quadrupole time-of-flight mass spectrometers (QTOF MS) may not provide. In this study, we evaluated the performance of a multi-reflecting time-of-flight (MRT) mass spectrometer for dual-isotope SIRM using [U-13C5,15N2]glutamine-infused patient-derived tumor xenografts and compared its performance with that of a conventional SYNAPT™ XS QTOF Platform operated at a resolving power of approximately 15,000. A total of 113 metabolites were detected on both platforms, and dual-isotope labeling patterns were evaluated for 29 carbon- and nitrogen-containing metabolites. The Xevo™ MRT Mass Spectrometer, operating at a resolving power of approximately 100,000, resolved closely spaced 13C- and 15N isotopologues that remained unresolved on the SYNAPT™ XS Instrument under the acquisition conditions used. This separation enabled composition-specific isotopologue assignment, independent peak integration, natural-abundance correction, and isotopologue-specific fractional-enrichment analysis. The higher sensitivity of Xevo™ MRT Mass Spectrometer improved detection of low-abundance isotopologues, increasing isotopologue coverage when compared to SYNAPT™ XS MS Instrument. Together, these results demonstrate that MRT-TOF mass spectrometry provides a practical high-resolution platform for dual-isotope SIRM and enables simultaneous assessment of carbon incorporation and nitrogen-transfer reactions within a single experiment.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine",
    "University of Louisville",
    "UofL Health-Brown Cancer Center, University of Louisville",
    "Waters Corporation"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Maleesha De Silva"
    },
    {
      "affs": [
        2,
        0,
        1
      ],
      "name": "Yoannis Imbert‑Fernandez"
    },
    {
      "affs": [
        2,
        0,
        1
      ],
      "name": "Brian F. Clem"
    },
    {
      "affs": [
        3
      ],
      "name": "Steven Lai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Pawel Lorkiewicz",
      "orcid": "0000-0002-1755-9826"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eqkq7e68ye918.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010430/v1",
  "fulltext_url": null,
  "id": "eqkq7e68ye918",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010430/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Metabolomics and Mass Spectrometry Studies"
    ]
  ],
  "openalex": "W7221782404",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010430/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/eqkq7e68ye918.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010430",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010430/v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolomics and Mass Spectrometry Studies",
      "subfield": "molecular-biology"
    }
  ],
  "title": "High-Resolution MRT-TOF Mass Spectrometry Enables Simultaneous Carbon and Nitrogen Tracing in Stable Isotope Resolved Metabolomics",
  "title_text": "High-Resolution MRT-TOF Mass Spectrometry Enables Simultaneous Carbon and Nitrogen Tracing in Stable Isotope Resolved Metabolomics",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/eqkq7e68ye918",
  "venue": "ChemRxiv",
  "versions": []
}