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Derivatives were already found on the drug of abuse market, such as\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>1<\/jats:sup>\n                    -\n                    <jats:italic>tert<\/jats:italic>\n                    -butoxycarbonyl-\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    -dimethyltryptamine (DMT-Boc). The aim of the current study was to investigate the toxicokinetics of DMT-Boc and three related DMT derivatives, by name DMT-isopropylcarbamate, DMT-pivaloylamide, and DMT-THP (\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    -dimethyl-2-[1-(oxan-2-yl)indol-3-yl]ethanamine). In vitro and in vivo metabolism studies with pooled human liver S9 incubations and zebrafish embryos were performed, respectively. Monooxygenase and monoamine oxidase (MAO) isozymes involved in the phase I metabolism were identified. In vitro metabolic stability and plasma protein binding (PPB) were evaluated. A total of 11 metabolites for DMT-Boc, 13 for DMT-isopropylcarbamate, eight for DMT-pivaloylamide and 16 for DMT-THP were identified using high-resolution tandem mass spectrometry.\n                    <jats:italic>N<\/jats:italic>\n                    -Demethylation and hydroxylation were the most relevant metabolic reactions. CYP1A2, CYP2D6, and FMO3 were identified as most active phase I isozymes and MAO-A contributed to DMT-THP metabolism. The in vitro half-lives of DMT-Boc, DMT-isopropylcarbamate, and DMT-pivaloylamide were calculated to be between 74 and 79\u00a0min, while that of DMT-THP was found to be &gt;\u2009180\u00a0min. All compounds showed high PPB (&gt;\u200999%) indicating that co-consumption with other drugs might increase the DMT derivatives\u2019 toxicity. Combined in vitro and in vivo approaches provided a comprehensive metabolism overview.\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N-bis<\/jats:italic>\n                    -Demethylated,\n                    <jats:italic>N<\/jats:italic>\n                    -demethylated and\n                    <jats:italic>N<\/jats:italic>\n                    -oxygenated metabolites along with parent compound were proposed as consumption markers in order to support clinical and forensic toxicologists to identify these substances in biosamples in case of suspected abuse.\n                  <\/jats:p>","DOI":"10.1007\/s00204-026-04552-3","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:48:20Z","timestamp":1790016500000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicokinetics and analytical toxicology of four N, N-dimethyltryptamine derivatives studied in human in vitro systems and in vivo by means of zebrafish embryos"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4259-0836","authenticated-orcid":false,"given":"Gloria","family":"Daziani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-7912","authenticated-orcid":false,"given":"Lea","family":"Wagmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias D.","family":"Kroesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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