{
  "abstract": "Electrospray ionization mass spectrometry (ESI-MS) is a standard and robust technique for analysis of a large variety of biomolecules. Direct infusion approaches offer rapid, high-throughput analysis of small sample volumes but are inherently susceptible to matrix effects during electrospray ionization. These matrix effects can substantially alter analyte ionization and gas-phase response and thereby complicate the interpretation of analyte abundances in complex biological samples. Herein, we developed a titration-based workflow to identify matrix effects and distinguish true changes in endogenous analyte abundance from ionization artifacts using direct infusion probe mass spectrometry (DIP-MS). Rat brain tissue extracts, rat insulinoma cell extracts, and isotopically labeled internal standards were used to model different matrix complexities to define condition-based differences in matrix effects. Thereafter, by mixing paired extracts in different ratios and fitting linear regression models, we assessed analyte-specific responses to sample-specific matrices. Moreover, we uncovered ion suppression or enhancement of hundreds of analytes by comparing regression slopes using interaction tests. We find that using endogenous analytes in our titration-based workflow gives a good indication of matrix effects for certain analyte classes. However, using a preselected panel of internal standards is strongly favorable for reliably identifying matrix effects during ionization. Altogether, combining our titration workflow, a selected panel of internal standards, and regression modeling provides a sensitive way of detecting matrix effects and for distinguishing true metabolite abundance changes from ionization artifacts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry for Life Sciences, Uppsala University, 752 37 Uppsala, Sweden",
    "Center of Excellence for the Chemical Mechanisms of Life, Uppsala University, 752 37 Uppsala, Sweden"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pontus Persson"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gabor Toth",
      "orcid": "0000-0003-1428-7906"
    },
    {
      "affs": [
        0
      ],
      "name": "Natália Remper"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucie Davidová",
      "orcid": "0009-0002-9918-5414"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ingela Lanekoff",
      "orcid": "0000-0001-9040-3230"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4gkf05eyedqay.bib",
  "cited_by": 0,
  "doi": "10.1021/jasms.6c00220",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13741900/",
  "id": "4gkf05eyedqay",
  "issns": [
    "1044-0305",
    "1879-1123"
  ],
  "landing_url": "https://doi.org/10.1021/jasms.6c00220",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1607|Mass Spectrometry Techniques and Applications"
    ]
  ],
  "openalex": "W7223456584",
  "pdf_url": "https://pubs.acs.org/jamsef/article-pdf/doi/10.1021/jasms.6c00220/68973603/jasms.6c00220.pdf",
  "pmcid": "PMC13741900",
  "pmid": "42980302",
  "published": "2026-10-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4gkf05eyedqay.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:22:51Z",
      "native_id": "PMC13741900",
      "source": "pmc",
      "url": "https://doi.org/10.1021/jasms.6c00220"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Mass Spectrometry Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Titration-Based Assessment of Matrix Effects in Direct Infusion Mass Spectrometry",
  "title_text": "Titration-Based Assessment of Matrix Effects in Direct Infusion Mass Spectrometry",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:22:51Z",
  "url": "https://research.draconitic.com/paper/4gkf05eyedqay",
  "venue": "Journal of the American Society for Mass Spectrometry",
  "versions": []
}