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Finally, metabolites were confirmed by human microdosing (HMD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ZEs 4 days post fertilization were exposed via immersion in Danieau's medium containing the compound or by injection into the caudal vein. After euthanization and freeze\u2010drying, the ZEs were extracted using methanol. HMD was performed by oral administration of individual compound solutions according to HMD guidelines. Urine was collected spontaneously over 24\u2009h and extracted via solid\u2010phase extraction with and without conjugate cleavage. Samples were then analysed using reversed\u2010phase liquid chromatography coupled to high resolution tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, both ZE and HMD allowed identification of main human urine metabolites as described in literature. Exceptions for HMD were LSD due to the low applied dose and the cannabinoids, probably due to low oral bioavailability. Furthermore, ZE generally produced more metabolites compared to HMD, including conjugates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The proposed workflow of ZE exposure followed by HMD can provide quick and reliable data for prediction of analytical biomarkers for urinary drug screening. Following the initial identification of metabolites in ZE, human metabolites can afterwards be confirmed by HMD study. However, there are still challenges regarding HMD such as different routes of administration and detectability of applied low doses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70140","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T01:15:51Z","timestamp":1750122951000},"source":"Crossref","is-referenced-by-count":2,"title":["Metabolic fate of drugs of abuse and new psychoactive substances: A pilot study on a novel workflow using a zebrafish embryo model combined with human microdosing"],"prefix":"10.1002","author":[{"given":"Simon K.","family":"Wellenberg","sequence":"first","affiliation":[{"name":"Experimental and Clinical Toxicology and Pharmacology, Center for Molecular Signaling (PZMS), PharmaScienceHub (PSH) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja M.","family":"Gampfer","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Toxicology and Pharmacology, Center for Molecular Signaling (PZMS), PharmaScienceHub (PSH) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-7912","authenticated-orcid":false,"given":"Lea","family":"Wagmann","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Toxicology and Pharmacology, Center for Molecular Signaling (PZMS), PharmaScienceHub (PSH) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Schippers","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Toxicology and Pharmacology, Center for Molecular Signaling (PZMS), PharmaScienceHub (PSH) Saarland University  Homburg Germany"},{"name":"Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland Saarland University  Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland Saarland University  Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland Saarland University  Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folker","family":"Westphal","sequence":"additional","affiliation":[{"name":"State Bureau of Criminal Investigation Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-6784","authenticated-orcid":false,"given":"Markus R.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Toxicology and Pharmacology, Center for Molecular Signaling (PZMS), PharmaScienceHub (PSH) Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.168"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2022.1033733"},{"key":"e_1_2_11_4_1","volume-title":"ICH guideline M3(R2) on non\u2010clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals","author":"EMA","year":"2009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2018_110"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.10.171"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2018.06.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2017.04.003"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2011.06.121"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.00539"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2019.01.010"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2024.116187"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkaa010"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25194474"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010018\u20105119\u2010x"},{"key":"e_1_2_11_16_1","unstructured":"EUDA.Cannabis drug profile. 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