{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:16:19Z","timestamp":1786947379622,"version":"build-2736575974"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jagiellonian University Medical College","award":["N41\/DBS\/000904"],"award-info":[{"award-number":["N41\/DBS\/000904"]}]},{"name":"Jagiellonian University Medical College","award":["N41\/DBS\/000800"],"award-info":[{"award-number":["N41\/DBS\/000800"]}]},{"name":"Jagiellonian University Medical College","award":["N42\/DBS\/000006"],"award-info":[{"award-number":["N42\/DBS\/000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Legal highs present a great threat to health, especially in groups of people experimenting with psychoactive substances. The lack of available knowledge on the biotransformation of these substances necessitates symptomatic treatment in the event of intoxication, which, unfortunately, may be ineffective. Opioids, including heroin analogues, such as U-47700, constitute a special group of designer drugs. In this study, a multi-directional approach to trace the biotransformation of U-47700 in living organisms was used. For this purpose, the in silico assessment (ADMET Predictor) was used first and then followed by an in vitro study using human liver microsomes and the S9 fraction. The biotransformation was then followed in an animal model (Wistar rats). Tissues such as blood, brain and liver were collected for analysis. The study was performed using liquid chromatography with tandem mass spectrometry (LC-MS\/MS). The obtained results were compared to those obtained from the analysis of autopsy materials (cases analysed in the Toxicology Laboratory of the Department of Forensic Medicine, Jagiellonian University Medical College in Krakow).<\/jats:p>","DOI":"10.3390\/toxics11030220","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:10:46Z","timestamp":1677463846000},"page":"220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic Evaluation of Synthetic Opioids on the Example of U-47700 with the Use of In Vitro and In Vivo Methods for Forensic Toxicology Application"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3188-0982","authenticated-orcid":false,"given":"Sebastian","family":"Rojek","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, Faculty of Medicine, Jagiellonian University Medical College, Grzeg\u00f3rzecka 16 Str., 31-531 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-5827","authenticated-orcid":false,"given":"Ewa","family":"Polja\u0144ska","sequence":"additional","affiliation":[{"name":"Toxicology Research Group, Department of Toxicology, Jagiellonian University Medical College, Medyczna 9 Str., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Chaim","sequence":"additional","affiliation":[{"name":"Toxicology Research Group, Department of Toxicology, Jagiellonian University Medical College, Medyczna 9 Str., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Maci\u00f3w-G\u0142\u0105b","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Faculty of Medicine, Jagiellonian University Medical College, Grzeg\u00f3rzecka 16 Str., 31-531 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6501-8656","authenticated-orcid":false,"given":"Beata","family":"Bystrowska","sequence":"additional","affiliation":[{"name":"Department of Biochemical Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Str., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/1556-4029.14268","article-title":"Prodrugs of New Psychoactive Substances (NPS): A New Challenge","volume":"65","author":"Elliott","year":"2020","journal-title":"J. Forensic Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2017.10.016","article-title":"Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review","volume":"134","author":"Armenian","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3389\/fpsyt.2017.00110","article-title":"An expanding world of Novel Psychoactive Substances: Opioids","volume":"8","year":"2017","journal-title":"Front. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.3389\/fphar.2018.01210","article-title":"Postmortem Toxicology of New Synthetic Opioids","volume":"9","author":"Concheiro","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.brainresbull.2020.11.017","article-title":"Psychopharmacological characterization of an emerging drug of abuse, a synthetic opioid U-47700, in adult zebrafish","volume":"167","year":"2021","journal-title":"Brain Res. Bull."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108195","DOI":"10.1016\/j.neuropharm.2020.108195","article-title":"Pharmacodynamics and pharmacokinetics of the novel synthetic opioid, U-47700, in male rats","volume":"177","author":"Truver","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Baumann, M.H., Tocco, G., Papsun, D.M., Mohr, A.L., Fogarty, M.F., and Krotulski, A.J. (2020). U-7700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market. Brain Sci., 10.","DOI":"10.3390\/brainsci10110895"},{"key":"ref_8","first-page":"173","article-title":"Analysis of U-47700, a novel synthetic opioid, in human urine by LC\u2013MS\u2013MS and LC\u2013QToF","volume":"41","author":"Fleming","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_9","unstructured":"(2023, January 30). European Drug Report 2022: Trends and Developments. Available online: www.emcdda.europa.eu\/publications\/edr\/trends-developments\/2022_en."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1449","DOI":"10.1002\/wfs2.1449","article-title":"Untargeted metabolomics approaches to improve casework in clinical and forensic toxicology\u2014\u201cWhere are we standing and where are we heading?\u201d","volume":"4","author":"Steuer","year":"2022","journal-title":"Wiley Interdiscip. Rev. Forensic Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s11419-019-00464-3","article-title":"Quantification of U-47700 and its metabolites: N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 in 12 autopsy blood samples employing SPE\/LC\u2013ESI-MS-MS","volume":"37","author":"Rojek","year":"2019","journal-title":"Forensic Toxicol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuropharm.2017.08.016","article-title":"Pharmacological characterization of novel synthetic opioids (NSO) found in the recreational drug marketplace","volume":"134","author":"Baumann","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11419-018-0454-5","article-title":"The search for the \u201cnext\u201d euphoric non-fentanil novel synthetic opioids on the illicit drugs market: Current status and horizon scanning","volume":"37","author":"Sharma","year":"2019","journal-title":"Forensic Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e116","DOI":"10.1093\/jat\/bkac023","article-title":"Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017\u20132020: A Review","volume":"46","author":"Mohr","year":"2022","journal-title":"J. Anal. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.toxlet.2019.01.010","article-title":"Tools for studying the metabolism of new psychoactive substances for toxicological screening purposes\u2014A comparative study using pooled human liver S9, HepaRG cells, and zebrafish larvae","volume":"305","author":"Richter","year":"2019","journal-title":"Toxicol Lett."},{"key":"ref_16","first-page":"121","article-title":"Metabolism testing methods as exemplified by selected new psychoactive substances (NPSs)","volume":"126","author":"Piechaczek","year":"2021","journal-title":"Probl. Forensic Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.toxlet.2020.04.001","article-title":"Are pigs a suitable animal model for in vivo metabolism studies of new psychoactive substances? A comparison study using different in vitro\/in vivo tools and U-47700 as model drug","volume":"329","author":"Nordmeier","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1007\/s00204-021-03169-y","article-title":"Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: Is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?","volume":"95","author":"Nordmeier","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/dta.3182","article-title":"Are the N-demethylated metabolites of U-47700 more active than their parent compound? In vitro \u03bc-opioid receptor activation of N-desmethyl-U-47700 and N, N-bisdesmethyl-U-47700","volume":"14","author":"Nordmeier","year":"2022","journal-title":"Drug Test Anal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/jat\/bkab044","article-title":"Perimortem Distribution of U-47700, Tramadol and Their Main Metabolites in Pigs Following Intravenous Administration","volume":"46","author":"Nordmeier","year":"2022","journal-title":"J. Anal. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/dta.2228","article-title":"Metabolism of novel opioid agonists U-47700 and U-49900 using human liver microsomes with confirmation in authentic urine specimens from drug users","volume":"10","author":"Krotulski","year":"2018","journal-title":"Drug Test Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jchromb.2019.02.026","article-title":"Quantification of U-47700 and its metabolites in plasma by LC-MS\/MS","volume":"1112","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109999","DOI":"10.1016\/j.forsciint.2019.109999","article-title":"Distribution of synthetic opioids in postmortem blood, vitreous humor and brain","volume":"305","author":"Chesser","year":"2019","journal-title":"Forensic Sci. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/jat\/bkaa157","article-title":"Heroin-Related Compounds and Metabolic Ratios in Postmortem Samples Using LC-MS-MS","volume":"45","author":"Jakobsson","year":"2021","journal-title":"J. Anal. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/20961790.2019.1588933","article-title":"Novel synthetic opioids-toxicological aspects and analysis","volume":"4","author":"Tabarra","year":"2019","journal-title":"Forensic Sci. 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