{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:12:25Z","timestamp":1790622745575,"version":"4.1.0"},"reference-count":111,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA000523-13"],"award-info":[{"award-number":["DA000523-13"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The recreational use of opioid drugs is a global threat to public health and safety. In particular, an epidemic of opioid overdose fatalities is being driven by illicitly manufactured fentanyl, while novel synthetic opioids (NSOs) are appearing on recreational drug markets as standalone products, adulterants in heroin, or ingredients in counterfeit drug preparations. Trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) is a prime example of a non-fentanyl NSO that is associated with numerous intoxications and fatalities. Here, we review the medicinal chemistry, preclinical pharmacology, clandestine availability, methods for detection, and forensic toxicology of U-47700 and its analogs. An up-to-date summary of the human cases involving U-47700 intoxication and death are described. The evidence demonstrates that U-47700 is a potent \u03bc-opioid receptor agonist, which poses a serious risk for overdosing and death. However, most analogs of U-47700 appear to be less potent and have been detected infrequently in forensic specimens. U-47700 represents a classic example of how chemical entities from the medicinal chemistry or patent literature can be diverted for use in recreational drug markets. Lessons learned from the experiences with U-47700 can inform scientists, clinicians, and policymakers who are involved with responding to the spread and impact of NSOs.<\/jats:p>","DOI":"10.3390\/brainsci10110895","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T08:18:23Z","timestamp":1606119503000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["U-47700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market"],"prefix":"10.3390","volume":"10","author":[{"given":"Michael H.","family":"Baumann","sequence":"first","affiliation":[{"name":"Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 333 Cassell Drive, Suite 4400, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0081-5704","authenticated-orcid":false,"given":"Graziella","family":"Tocco","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Papsun","sequence":"additional","affiliation":[{"name":"Toxicology Department, NMS Labs, 200 Welsh Road, Horsham, PA 19044, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda L.","family":"Mohr","sequence":"additional","affiliation":[{"name":"Center for Forensic Science Research and Education, Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, 19090 PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa F.","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Center for Forensic Science Research and Education, Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, 19090 PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-1882","authenticated-orcid":false,"given":"Alex J.","family":"Krotulski","sequence":"additional","affiliation":[{"name":"Center for Forensic Science Research and Education, Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, 19090 PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"ref_1","unstructured":"United Nations Office on Drugs and Crime (2020, August 01). World Drug Report 2020. Available online: https:\/\/wdr.unodc.org\/wdr2020\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1373\/clinchem.2017.281626","article-title":"The Fentanyl Epidemic and Evolution of Fentanyl Analogs in the United States and the European Union","volume":"65","author":"Jannetto","year":"2019","journal-title":"Clin. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Han, Y., Yan, W., Zheng, Y., Khan, M.Z., Yuan, K., and Lu, L. (2019). The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies. Transl. Psychiatry, 9.","DOI":"10.1038\/s41398-019-0625-0"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Frisoni, P., Bacchio, E., Bilel, S., Talarico, A., Gaudio, R.M., Barbieri, M., Neri, M., and Marti, M. (2018). Novel Synthetic Opioids: The Pathologist\u2019s Point of View. Brain Sci., 8.","DOI":"10.3390\/brainsci8090170"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/ADM.0000000000000324","article-title":"Misuse of Novel Synthetic Opioids: A Deadly New Trend","volume":"11","author":"Prekupec","year":"2017","journal-title":"J. Addict. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/164_2018_149","article-title":"Synthetic Opioids","volume":"252","author":"Beardsley","year":"2018","journal-title":"Handb. Exp. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.tips.2018.09.006","article-title":"Pharmacological Research as a Key Component in Mitigating the Opioid Overdose Crisis","volume":"39","author":"Baumann","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jat\/bky049","article-title":"The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response","volume":"43","author":"Morrow","year":"2019","journal-title":"J. Anal. Toxicol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/npp.2017.211","article-title":"Novel Synthetic Opioids and Overdose Deaths: Tip of the Iceberg?","volume":"43","author":"Baumann","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1021\/jm00326a001","article-title":"Stereochemical studies on medicinal agents. II. absolute configuration of (--)-phenampromide","volume":"8","author":"Portoghese","year":"1965","journal-title":"J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1021\/jm00246a014","article-title":"Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1","volume":"18","author":"Natsuka","year":"1975","journal-title":"J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Natsuka, K., Nakamura, H., Nishikawa, Y., Negoro, T., Uno, H., and Nishimura, H. (1987). Synthesis and structure-activity relationships of 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives having narcotic agonist and antagonist activity. J. Med. Chem., 30.","DOI":"10.1021\/jm00393a017"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1021\/jm00257a012","article-title":"1-(3,4-Dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesics","volume":"17","author":"Harper","year":"1974","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s11419-015-0271-z","article-title":"AH-7921: The list of new psychoactive opioids is expanded","volume":"33","author":"Katselou","year":"2015","journal-title":"Forensic Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1021\/jm00150a017","article-title":"Factors affecting binding of trans-N-[2-(methylamino)cyclohexyl]benzamides at the primary morphine receptor","volume":"28","author":"Cheney","year":"1985","journal-title":"J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1021\/jm00352a005","article-title":"Benzeneacetamide amines: Structurally novel non-m mu opioids","volume":"25","author":"Szmuszkovicz","year":"1982","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/0024-3205(82)90132-1","article-title":"Properties of a selective kappa agonist, U-50,488H","volume":"31","author":"Lahti","year":"1982","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0278-5846(82)80130-9","article-title":"U-50,488, a selective kappa opioid agonist: Comparison to other reputed kappa agonists","volume":"6","author":"Lewis","year":"1982","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","unstructured":"Kyei-Baffour, K., and Lindsley, C.W. (2020). DARK Classics in Chemical Neuroscience: U-47700. ACS Chem. Neurosci.","DOI":"10.1021\/acschemneuro.0c00330"},{"key":"ref_22","unstructured":"(2020, October 14). Gray Death Drug Facts: Effects, Hazards & Warnings. Available online: https:\/\/www.drugs.com\/illicit\/graydeath.html."},{"key":"ref_23","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","author":"Zawilska","year":"2017","journal-title":"Front. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1016\/j.forsciint.2019.04.010","article-title":"Postmortem concentrations of the synthetic opioid U-47700 in 26 fatalities associated with the drug","volume":"301","author":"Fels","year":"2019","journal-title":"Forensic Sci. Int."},{"key":"ref_25","first-page":"709","article-title":"Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC-MS\/MS in Postmortem Casework","volume":"40","author":"Mohr","year":"2016","journal-title":"J. Anal. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1093\/jat\/bkx081","article-title":"U-47700: A Not So New Opioid","volume":"42","author":"Rohrig","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_27","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","author":"Smith","year":"2019","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jemermed.2017.05.034","article-title":"U-47700: A Clinical Review of the Literature","volume":"53","author":"Rambaran","year":"2017","journal-title":"J. Emerg. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-3-0348-9146-2_6","article-title":"Medicinal agents incorporating the 1,2-diamine functionality","volume":"33","author":"Michalson","year":"1989","journal-title":"Prog. Drug Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/978-3-0348-8730-4_4","article-title":"U-50,488 and the kappa receptor: A personalized account covering the period 1973 to 1990","volume":"52","author":"Szmuszkovicz","year":"1999","journal-title":"Prog. Drug Res."},{"key":"ref_31","first-page":"7","article-title":"U-50,488: A selective and structurally novel non-Mu (kappa) opioid agonist","volume":"224","author":"Vonvoigtlander","year":"1983","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6338","DOI":"10.1038\/s41598-017-06778-9","article-title":"Updating the list of known opioids through identification and characterization of the new opioid derivative 3,4-dichloro-N-(2-(diethylamino)cyclohexyl)-N-methylbenzamide (U-49900)","volume":"7","author":"Ventura","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.1021\/jm9803166","article-title":"Conformational analysis and automated receptor docking of selective arylacetamide-based kappa-opioid agonists","volume":"41","author":"Subramanian","year":"1998","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/s10517-015-3057-8","article-title":"Prospects of Using of \u03ba-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia\/Reperfusion","volume":"159","author":"Tsibulnikov","year":"2015","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_35","first-page":"144","article-title":"Structure activity studies of two classes of beta-amino-amides: The search for kappa-selective opioids","volume":"90","author":"Loew","year":"1988","journal-title":"NIDA Res. Monogr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1021\/jm00105a061","article-title":"(2S)-1-(arylacetyl)-2-(aminomethyl)piperidine derivatives: Novel, highly selective kappa opioid analgesics","volume":"34","author":"Vecchietti","year":"1991","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Clark, C.R., Halfpenny, P.R., Hill, R.G., Horwell, D.C., Hughes, J., Jarvis, T.C., Rees, D.C., and Schofield, D. (1988). Highly selective kappa opioid analgesics. Synthesis and structure-activity relationships of novel N-[(2-aminocyclohexyl)aryl]acetamide and N-[(2-aminocyclohexyl)aryloxy]acetamide derivatives. J. Med. Chem., 31.","DOI":"10.1021\/jm00399a025"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1021\/jm00128a050","article-title":"Alterations in the stereochemistry of the kappa-selective opioid agonist U50,488 result in high-affinity sigma ligands","volume":"32","author":"Bowen","year":"1989","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00511","DOI":"10.1002\/prp2.511","article-title":"Synthesis and pharmacological characterization of ethylenediamine synthetic opioids in human \u03bc-opiate receptor 1 (OPRM1) expressing cells","volume":"7","author":"Hsu","year":"2019","journal-title":"Pharm. Res. Perspect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1021\/jm00114a015","article-title":"Synthesis and receptor binding of enantiomeric N-substituted cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamines as high-affinity sigma receptor ligands","volume":"34","author":"Radesca","year":"1991","journal-title":"J. Med. Chem."},{"key":"ref_41","first-page":"259","article-title":"Analgesic and mechanistic evaluation of spiradoline, a potent kappa opioid","volume":"246","author":"VonVoigtlander","year":"1988","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1527-3458.2003.tb00248.x","article-title":"A Review of the Properties of Spiradoline: A Potent and Selective k-Opioid Receptor Agonist","volume":"9","author":"Wadenberg","year":"2003","journal-title":"CNS Drug Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuropharm.2013.03.039","article-title":"Opioids and their receptors: Are we there yet?","volume":"76","author":"Pasternak","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_44","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_45","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_46","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00414-018-1969-3","article-title":"Case report: Relevance of metabolite identification to detect new synthetic opioid intoxications illustrated by U-47700","volume":"133","author":"Richeval","year":"2019","journal-title":"Int. J. Leg. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1002\/dta.2683","article-title":"Toxicokinetics and analytical toxicology of the abused opioid U-48800-in vitro metabolism, metabolic stability, isozyme mapping, and plasma protein binding","volume":"11","author":"Gampfer","year":"2019","journal-title":"Drug Test. Anal."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Koch, K., Auw\u00e4rter, V., Hermanns-Clausen, M., Wilde, M., and Neukamm, M.A. (2018). Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data. Drug Test. Anal.","DOI":"10.1002\/dta.2391"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.addr.2007.05.015","article-title":"Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development","volume":"59","author":"Mahmood","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"180","DOI":"10.2174\/1389201019666180509164240","article-title":"Non-fatal Overdose with U-47700: Identification in Biological Matrices","volume":"19","author":"Vogliardi","year":"2018","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/1556-4029.13903","article-title":"Near-fatal Intoxication with the \u201cNew\u201d Synthetic Opioid U-47700: The First Reported Case in the Czech Republic","volume":"64","author":"Horsley","year":"2019","journal-title":"J. Forensic Sci."},{"key":"ref_53","unstructured":"Jorge, R. (2016). EU Early Warning System Alert: U-47,700 in Europe."},{"key":"ref_54","unstructured":"World Health Organization (2020, August 01). Expert Committee on Drug Dependence; U-47700 Critical Review Report. Available online: https:\/\/www.who.int\/medicines\/access\/controlled-substances\/4.1_U-47700_CritReview.pdf."},{"key":"ref_55","unstructured":"Drug Enforcement Administration: Strategic Intelligence Section (2020, August 01). Counterfeit Prescription Pills Containing Fentanyls, A Global Threat, Available online: https:\/\/www.hsdl.org\/?view&did=796541."},{"key":"ref_56","unstructured":"Drug Enforcement Administration: Special Testing and Research Laboratory (2020, August 01). DEA Emerging Threat Report First Quarter. Available online: https:\/\/cesar.umd.edu\/publicationprofile\/193."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.15585\/mmwr.mm6641a6","article-title":"Notes from the Field: Counterfeit Percocet-Related Overdose Cluster\u2014Georgia, June 2017","volume":"66","author":"Edison","year":"2017","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/1556-4029.14237","article-title":"Seizures of Clandestinely Produced Tablets in Santa Catarina, Brazil: The Increase in NPS from 2011 to 2017","volume":"65","author":"Filho","year":"2020","journal-title":"J. Forensic Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15563650.2016.1217003","article-title":"New Psychoactive Substances (NPS)\u2014the Hydra monster of recreational drugs","volume":"55","author":"Helander","year":"2017","journal-title":"Clin. Toxicol. (Phila)"},{"key":"ref_60","unstructured":"Drug Enforcement Administration (2020, August 01). Diversion Control Office Tracking Fentanyl and Fentanyl-Related Substances Reported in NFLIS-Drug by State, 2016\u20132017, Available online: https:\/\/www.nflis.deadiversion.usdoj.gov\/DesktopModules\/ReportDownloads\/Reports\/NFLISDrugSpecialRelease-Fentanyl-FentanylSubstancesStateMaps-2016-2017.pdf."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pop\u0142awska, M., Bednarek, E., Naumczuk, B., Kozerski, L., and B\u0142a\u017cewicz, A. (2020). Identification and structure characterization of five synthetic opioids: 3,4-methylenedioxy-U-47700, o-methyl-acetylfentanyl, 2-thiophenefentanyl, benzoylfentanyl and benzoylbenzylfentanyl. Forensic Toxicol.","DOI":"10.1007\/s11419-020-00539-6"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/jat\/bkx108","article-title":"A Validated Method for the Screening of 320 Forensically Significant Compounds in Blood by LC\/QTOF, with Simultaneous Quantification of Selected Compounds","volume":"42","author":"Partridge","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/jat\/bks084","article-title":"Validation of LC-TOF-MS screening for drugs, metabolites, and collateral compounds in forensic toxicology specimens","volume":"37","author":"Guale","year":"2013","journal-title":"J. Anal. Toxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"135","DOI":"10.33176\/AACB-19-00023","article-title":"Quadrupole Time-of-Flight Mass Spectrometry: A Paradigm Shift in Toxicology Screening Applications","volume":"40","author":"Allen","year":"2019","journal-title":"Clin. Biochem. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5821","DOI":"10.1007\/s00216-017-0441-4","article-title":"Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: A critical review","volume":"409","author":"Pasin","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trac.2018.01.007","article-title":"New synthetic opioids in biological and non-biological matrices: A review of current analytical methods","volume":"102","author":"Marchei","year":"2018","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/1556-4029.14184","article-title":"Sample Mining and Data Mining: Combined Real-Time and Retrospective Approaches for the Identification of Emerging Novel Psychoactive Substances","volume":"65","author":"Krotulski","year":"2020","journal-title":"J. Forensic Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.forsciint.2019.04.030","article-title":"Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by re-analysis of UPLC-TOF-MS data","volume":"300","author":"Kriikku","year":"2019","journal-title":"Forensic Sci. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1002\/dta.2393","article-title":"Analysis of fentanyl analogs and novel synthetic opioids in blood, serum\/plasma, and urine in forensic casework","volume":"10","author":"Moody","year":"2018","journal-title":"Drug Test. Anal."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1021\/acsomega.7b01536","article-title":"LC-MS\/MS-Based Method for the Multiplex Detection of 24 Fentanyl Analogues and Metabolites in Whole Blood at Sub ng mL-1 Concentrations","volume":"3","author":"Strayer","year":"2018","journal-title":"ACS Omega"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s11419-018-0458-1","article-title":"Quantification of seven novel synthetic opioids in blood using LC\u2013MS\/MS","volume":"37","author":"Lowry","year":"2019","journal-title":"Forensic Toxicol."},{"key":"ref_72","first-page":"173","article-title":"Analysis of U-47700, a Novel Synthetic Opioid, in Human Urine by LC-MS-MS and LC-QToF","volume":"41","author":"Fleming","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/jat.3962","article-title":"Screening procedure for 38 fentanyl analogues and five other new opioids in whole blood by liquid chromatography-tandem mass spectrometry","volume":"40","author":"Adamowicz","year":"2020","journal-title":"J. Appl. Toxicol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00216-018-1504-x","article-title":"A validated workflow for drug detection in oral fluid by non-targeted liquid chromatography-tandem mass spectrometry","volume":"411","author":"Reinstadler","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/dta.2868","article-title":"Development and validation of liquid chromatography-tandem mass spectrometry targeted screening of 16 fentanyl analogs and U-47700 in hair: Application to 137 authentic samples","volume":"12","author":"Larabi","year":"2020","journal-title":"Drug Test. Anal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/jat\/bky093","article-title":"Detection of Fentanyl Analogs and Synthetic Opioids in Real Hair Samples","volume":"43","author":"Salomone","year":"2019","journal-title":"J. Anal. Toxicol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s13181-017-0632-6","article-title":"A Novel Oral Fluid Assay (LC-QTOF-MS) for the Detection of Fentanyl and Clandestine Opioids in Oral Fluid After Reported Heroin Overdose","volume":"13","author":"Griswold","year":"2017","journal-title":"J. Med. Toxicol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3389\/fphar.2018.00747","article-title":"First Case in Italy of Fatal Intoxication Involving the New Opioid U-47700","volume":"9","author":"Gerace","year":"2018","journal-title":"Front. Pharm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.forsciint.2017.12.031","article-title":"The distribution and redistribution of fentanyl & norfentanyl in post mortem samples","volume":"284","author":"Chatterton","year":"2018","journal-title":"Forensic Sci. Int."},{"key":"ref_80","first-page":"158","article-title":"A Fatality Related to the Synthetic Opioid U-47700: Postmortem Concentration Distribution","volume":"41","author":"McIntyre","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_81","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_82","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. Pharm."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"110175","DOI":"10.1016\/j.forsciint.2020.110175","article-title":"Long-term stability of novel synthetic opioids in blood","volume":"308","author":"Truver","year":"2020","journal-title":"Forensic Sci. Int."},{"key":"ref_84","first-page":"86","article-title":"Challenges Related to Three Cases of Fatal Intoxication to Multiple Novel Synthetic Opioids","volume":"44","author":"Garneau","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Wadsworth, E., Drummond, C., and Deluca, P. (2018). The Dynamic Environment of Crypto Markets: The Lifespan of New Psychoactive Substances (NPS) and Vendors Selling NPS. Brain Sci., 8.","DOI":"10.3390\/brainsci8030046"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.15585\/mmwr.mm6643e1","article-title":"Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700\u201410 States, July-December 2016","volume":"66","author":"Halpin","year":"2017","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1111\/1556-4029.14114","article-title":"The Outbreak of Fentanyl-Related Deaths in Cook County, Illinois, Between October 2015 and December 2017: A Retrospective Study and a Comparison with Previous Data","volume":"64","author":"Serinelli","year":"2019","journal-title":"J. Forensic Sci."},{"key":"ref_88","unstructured":"(2020, October 22). 2016\u2014Final Order: Temporary Placement of U-47700 into Schedule I, Available online: https:\/\/www.deadiversion.usdoj.gov\/fed_regs\/rules\/2016\/fr1114.htm."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/20961790.2019.1588933","article-title":"Novel synthetic opioids\u2014toxicological aspects and analysis","volume":"4","author":"Tabarra","year":"2019","journal-title":"Forensic Sci. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/15563650.2016.1209764","article-title":"Near death from a novel synthetic opioid labeled U-47700: Emergence of a new opioid class","volume":"55","author":"Schneir","year":"2017","journal-title":"Clin. Toxicol. (Phila)"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/dta.1984","article-title":"The first reported fatality associated with the synthetic opioid 3,4-dichloro- N -[2-(dimethylamino)cyclohexyl]- N -methylbenzamide (U-47700) and implications for forensic analysis: First reported fatality involving the synthetic opioid U-47700","volume":"8","author":"Elliott","year":"2016","journal-title":"Drug Test. Anal."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.forsciint.2016.05.001","article-title":"A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700)","volume":"266","author":"Coopman","year":"2016","journal-title":"Forensic Sci. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1007\/s00414-017-1593-7","article-title":"Postmortem concentration distribution in fatal cases involving the synthetic opioid U-47700","volume":"131","author":"Dziadosz","year":"2017","journal-title":"Int. J. Leg. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"477","DOI":"10.23907\/2017.040","article-title":"Case Series of Novel Illicit Opioid-Related Deaths","volume":"7","author":"Papsun","year":"2017","journal-title":"Acad. Forensic Pathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/jat\/bkx060","article-title":"Multiple Drug-Toxicity Involving Novel Psychoactive Substances, 3-Fluorophenmetrazine and U-47700","volume":"41","author":"Ellefsen","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s12024-018-0018-3","article-title":"Another fatal case related to the recreational abuse of U-47700","volume":"14","author":"Strehmel","year":"2018","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/jat\/bky039","article-title":"A Case Study Involving U-47700, Diclazepam and Flubromazepam-Application of Retrospective Analysis of HRMS Data","volume":"42","author":"Partridge","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/jat\/bky035","article-title":"Analysis of Fentanyl and 18 Novel Fentanyl Analogs and Metabolites by LC-MS-MS, and report of Fatalities Associated with Methoxyacetylfentanyl and Cyclopropylfentanyl","volume":"42","author":"Fogarty","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/15563650.2016.1240806","article-title":"Synthetic agents off the darknet: A case of U-47700 and phenazepam abuse","volume":"55","author":"Vo","year":"2017","journal-title":"Clin. Toxicol. (Phila)"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jat\/bkx049","article-title":"Confirmation of Carfentanil, U-47700 and Other Synthetic Opioids in a Human Performance Case by LC\u2013MS-MS","volume":"41","author":"Seither","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/15563650.2016.1209767","article-title":"A case of U-47700 overdose with laboratory confirmation and metabolite identification","volume":"55","author":"Jones","year":"2017","journal-title":"Clin. Toxicol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.annemergmed.2016.06.014","article-title":"Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street \u201cNorco\u201d in Central California: A Case Report","volume":"69","author":"Armenian","year":"2017","journal-title":"Ann. Emerg. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1373\/jalm.2017.023028","article-title":"A Case of Opioid Overdose? Or Is It?","volume":"2","author":"French","year":"2018","journal-title":"J. Appl. Lab. Med."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Chapman, B.P., Lai, J.T., Krotulski, A.J., Fogarty, M.F., Griswold, M.K., Logan, B.K., and Babu, K.M. (2019). A Case of Unintentional Opioid (U-47700) Overdose in a Young Adult after Counterfeit Xanax Use. Pediatric Emerg. Care.","DOI":"10.1097\/PEC.0000000000001775"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1093\/jat\/bkx092","article-title":"Fatality Following Ingestion of Tetrahydrofuranylfentanyl, U-49900 and Methoxy-Phencyclidine","volume":"42","author":"Krotulski","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/15563650.2016.1209763","article-title":"Two cases of intoxication with new synthetic opioid, U-47700","volume":"55","author":"Domanski","year":"2017","journal-title":"Clin. Toxicol. (Phila)"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1093\/jat\/bky013","article-title":"Anodyne by Design; Measuring the Prevalence of Esoteric Designer Opioids in Pain Management Patients","volume":"42","author":"Goggin","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/dta.2738","article-title":"Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene","volume":"12","author":"Blanckaert","year":"2020","journal-title":"Drug Test. Anal."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/jat\/bkaa016","article-title":"Isotonitazene Quantitation and Metabolite Discovery in Authentic Forensic Casework","volume":"44","author":"Krotulski","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"ref_110","unstructured":"United Nations Office on Drugs and Crime (2020, August 01). Growing Complexity of the Opioid Crisis. Available online: https:\/\/opioidactioncenter.com\/resource\/united-nations-office-on-drugs-and-crime-the-growing-complexity-of-the-opioid-crisis\/."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1007\/s00204-020-02855-7","article-title":"In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances","volume":"94","author":"Vandeputte","year":"2020","journal-title":"Arch. Toxicol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/11\/895\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:36:01Z","timestamp":1760178961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/11\/895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":111,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["brainsci10110895"],"URL":"https:\/\/doi.org\/10.3390\/brainsci10110895","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]}}}