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NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. \u201cU compounds\u201d including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution.<\/jats:p><jats:p>After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography\u2013mass spectrometry and liquid chromatography\u2013mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned.<\/jats:p><jats:p>Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600\u00a0ng\/ml and 37\u00a0ng\/ml), tilidine and benzodiazepines. In case 2, U-47700 (204\u00a0ng\/ml) together with methadone (290\u00a0ng\/ml), flubromazepam (480\u00a0ng\/ml) and diazepam (300\u00a0ng\/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266\u00a0ng\/ml), furanylfentanyl (4.3\u00a0ng\/ml) 4-ANPP (15\u00a0ng\/ml) and alprazolam (69\u00a0ng\/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS\u2009=\u20093).<\/jats:p><jats:p>NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data.<\/jats:p>","DOI":"10.1007\/s00414-024-03263-7","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T22:01:41Z","timestamp":1717452101000},"page":"1801-1811","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intoxications involving methoxyacetylfentanyl and U-47700: a study of 3 polydrug fatalities"],"prefix":"10.1007","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0441-9787","authenticated-orcid":false,"given":"Arianna","family":"Giorgetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Gro\u00dfe Perdekamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Franchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Pircher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Pollak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susi","family":"Pelotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Auw\u00e4rter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"3263_CR1","doi-asserted-by":"publisher","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2023) European Drug Report 2023: trends and developments. https:\/\/www.emcdda.europa.eu\/publications\/european-drug-report\/2023_en. https:\/\/doi.org\/10.2810\/161905.\u00a0Accessed 9 Dec 2023","DOI":"10.2810\/161905"},{"key":"3263_CR2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1080\/02791072.1981.10471455","volume":"13","author":"WA Ayres","year":"1981","unstructured":"Ayres WA, Starsiak MJ, Sokolay P (1981) The bogus drug: Three methyl & alpha methyl fentanyl sold as \u201cChina White.\u201d J Psychoactive Drugs 13:91\u201393. https:\/\/doi.org\/10.1080\/02791072.1981.10471455","journal-title":"J Psychoactive Drugs"},{"key":"3263_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11419-018-0454-5","volume":"37","author":"KK Sharma","year":"2019","unstructured":"Sharma KK, Hales TG, Rao VJ, NicDaeid N, McKenzie C (2019) The search for the \u201cnext\u201d euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning. 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