Fast & fluorinated – Development and validation of a rapid benchtop NMR approach and other routine screening methods for the detection and quantification of synthesized fluorofentanyl derivatives

Mounteney, 2015, Fentanyls: are we missing the signs? Highly potent and on the rise in Europe, Int. J. Drug Policy, 26, 626, 10.1016/j.drugpo.2015.04.003 Suzuki, 2017, A review: fentanyl and non-pharmaceutical fentanyls, Drug Alcohol Depend., 171, 107, 10.1016/j.drugalcdep.2016.11.033 Armenian, 2018, Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review, Neuropharmacology, 134, 121, 10.1016/j.neuropharm.2017.10.016 Scholl, 2019, Drug and opioid-involved overdose deaths – United States, 2013–2017, MMWR Morb. Mortal. Wkly. Rep., 67, 1419 Lucyk, 2017, Novel synthetic opioids: an opioid epidemic within an opioid epidemic, Ann. Emerg. Med., 69, 91, 10.1016/j.annemergmed.2016.08.445 Armenian, 2017, Fentanyl and a novel synthetic opioid U-47700 masquerading as street “Norco” in Central California: a case report, Ann. Emerg. Med., 69, 87, 10.1016/j.annemergmed.2016.06.014 Frank, 2017, Addressing the fentanyl threat to public health, N. Engl. J. Med., 376, 605, 10.1056/NEJMp1615145 Rodda, 2017, A cluster of fentanyl-laced heroin deaths in 2015 in Melbourne, Australia, J. Anal. Toxicol., 41, 318, 10.1093/jat/bkx013 DeRienz, 2018, Child fatalities due to heroin/fentanyl exposure: what the case history missed, J. Anal. Toxicol., 42, 581, 10.1093/jat/bky052 Baldwin, 2018, Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths in British Columbia, Canada: an observational analysis, Drug Alcohol Depend., 185, 322, 10.1016/j.drugalcdep.2017.12.032 United Nations Office on Drugs and Crime, January 2020 – United Kingdom: ACMD Report on the Misuse of Fentanyl and Fentanyl Analogues as Global Number of Opioid NPS Rises, https://www.unodc.org/LSS/Announcement/Details/94dc6286-16bb-4e7a-9429-65d28918b332, 2020 (accessed 15 July 2020). Helland, 2017, Two hospitalizations and one death after exposure to ortho-fluorofentanyl, J. Anal. Toxicol., 41, 708, 10.1093/jat/bkx050 Finnish Medicines Agency, 2-Fluorofentanyl (N-(2-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl]-propanamide); 3-Fluorofentanyl (N-(3-fluorophenyl)-N-[1-(2-phenylethyl)piperidin-4-yl]-propanamide), http://ec.europa.eu/growth/tools-databases/tris/es/index.cfm/search/?trisaction=search.detail&year=2017&num=438&iLang=EN, 2017 (accessed 14 August 2019). Réseau Européen d'Information sur les Drogues et les Toxicomanies, Harms and Harm Reduction Workbook, https://en.ofdt.fr/BDD/publications/docs/France2017-3-4-Hhr-EN.pdf, 2017 (accessed 14 August 2019). Advisory Council on the Misuse of Drugs, Misuse of Fentanyl and Fentanyl Analogues, https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/855893/ACMD_Report_-_Misuse_of_fentanyl_and_fentanyl_analogues.pdf, 2020 (accessed 15 Jan 2020). Bäckberg, 2015, Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project, Clin. Toxicol., 53, 609, 10.3109/15563650.2015.1054505 Rojkiewicz, 2017, Identification and physicochemical characterization of 4-fluorobutyrfentanyl (1-((4-fluorophenyl)(1-phenethylpiperidin-4-yl)amino)butan-1-one, 4-FBF) in seized materials and post-mortem biological samples, Drug Test. Anal., 9, 405, 10.1002/dta.2135 Helander, 2017, Intoxications involving acrylfentanyl and other novel designer fentanyls – results from the Swedish STRIDA project, Clin. Toxicol., 55, 589, 10.1080/15563650.2017.1303141 Dussy, 2016, An acute ocfentanil fatality: a case report with postmortem concentrations, J. Anal. Toxicol., 40, 761 Liu, 2018, The identification and analytical characterization of 2,2′-difluorofentanyl, Drug Test. Anal., 10, 774, 10.1002/dta.2264 Spahn, 2017, A nontoxic pain killer designed by modeling of pathological receptor conformations, Science, 355, 966, 10.1126/science.aai8636 Kohyama, 2017, Analytical differentiation of quinolinyl- and isoquinolinyl-substituted 1-(5-fluoropentyl)-1H-indole-3-carboxylates: 5F-PB-22 and its ten isomers, Forensic Toxicol., 35, 56, 10.1007/s11419-016-0334-9 Chikumoto, 2019, Liquid chromatography–mass spectrometry studies on the isomeric 1-fluorobenzyl-3-naphthoyl-indoles: FUB-JWH-018 and five isomers, Forensic Toxicol., 37, 113, 10.1007/s11419-018-0442-9 Kusano, 2015, Positional isomer differentiation of synthetic cannabinoid JWH-081 by GC–MS/MS: Isomer differentiation of JWH-081 by GC–MS/MS, J. Mass Spectrom., 50, 586, 10.1002/jms.3565 Abiedalla, 2019, Spectroscopic differentiation and chromatographic separation of regioisomeric indole aldehydes: synthetic cannabinoids precursors, Forensic Chem., 12, 78, 10.1016/j.forc.2018.12.004 Nakazono, 2013, Differentiation of regioisomeric fluoroamphetamine analogs by gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry, Forensic Toxicol., 31, 241, 10.1007/s11419-013-0184-7 Negishi, 2015, Differentiation of regioisomeric chloroamphetamine analogs using gas chromatography–chemical ionization-tandem mass spectrometry, Forensic Toxicol., 33, 338, 10.1007/s11419-015-0280-y Takeda, 2017, Regioisomeric separation of ring-substituted cathinones by liquid chromatography–mass spectrometry with a naphthylethyl column, Forensic Toxicol., 35, 10.1007/s11419-016-0351-8 Stuhmer, 2020, Discrimination of seized drug positional isomers based on statistical comparison of electron-ionization mass spectra, Forensic Chem., 20, 100261, 10.1016/j.forc.2020.100261 Bonetti, 2018, Mass spectral differentiation of positional isomers using multivariate statistics, Forensic Chem., 9, 50, 10.1016/j.forc.2018.06.001 Davidson, 2019, The differentiation of 2,5-dimethoxy-N-(N-methoxybenzyl)phenethylamine (NBOMe) isomers using GC retention indices and multivariate analysis of ion abundances in electron ionization mass spectra, Forensic Chem., 14, 100160, 10.1016/j.forc.2019.100160 Gilbert, 2020, Classification of fentanyl analogues through principal component analysis (PCA) and hierarchical clustering of GC–MS data, Forensic Chem., 21, 100287, 10.1016/j.forc.2020.100287 Hussain, 2020, Quantification of MDMA in seized tablets using benchtop 1H NMR spectroscopy in the absence of internal standards, Forensic Chem., 20, 10.1016/j.forc.2020.100263 Assemat, 2017, Screening of “spice” herbal mixtures: from high-field to low-field proton NMR, Forensic Sci. Int., 279, 88, 10.1016/j.forsciint.2017.08.006 Antonides, 2019, Rapid identification of novel psychoactive and other controlled substances using low-field 1H NMR spectroscopy, ACS Omega, 4, 7103, 10.1021/acsomega.9b00302 Duffy, 2019, Differentiation of fentanyl analogues by low-field NMR spectroscopy, Anal. Chim. Acta, 1049, 161, 10.1016/j.aca.2018.12.014 Williams, 2010, Drying of organic solvents: quantitative evaluation of the efficiency of several desiccants, J. Org. Chem., 75, 8351, 10.1021/jo101589h Fulmer, 2010, NMR chemical shifts of trace impurities: common laboratory solvents, organics, and gases in deuterated solvents relevant to the organometallic chemist, Organometallics, 29, 2176, 10.1021/om100106e Yang, 2015, Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR, Nat. Commun., 6, 8202, 10.1038/ncomms9202 Pauli, 2014, Importance of purity evaluation and the potential of quantitative 1H NMR as a purity assay: miniperspective, J. Med. Chem., 57, 9220, 10.1021/jm500734a Gilbert, 2020, Hitting the Jackpot – development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 18 fentanyl‐derived synthetic opioids, Drug Test. Anal., 12, 798, 10.1002/dta.2771 McLaughlin, 2016, Test purchase, synthesis, and characterization of 2-methoxydiphenidine (MXP) and differentiation from its meta - and para -substituted isomers: characterization of 2-, 3- and 4-methoxydiphenidine isomers, Drug Test. Anal., 8, 98, 10.1002/dta.1800 United Nations Office on Drugs and Crime, Rapid Testing Methods of Drugs of Abuse, https://www.unodc.org/documents/scientific/Rapid_Testing_Methods_of_Drugs_of_Abuse_E.pdf, 1995 (accessed 06 July 2019). K.-A. Kovar, M. Laudszun, Chemistry and Reaction Mechanisms of Rapid Tests for Drugs of Abuse and Precursors Chemicals. https://www.unodc.org/pdf/scientific/SCITEC6.pdf, 1989 (accessed 06 July 2019). Kangas, 2017, A new possible alternative colorimetric drug detection test for fentanyl, Org. Med. Chem. Int. J., 4 Geyer, 2016, Guilty by dissociation – development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 13 diphenidine-derived new psychoactive substances (NPSs), Anal. Bioanal. Chem., 408, 8467, 10.1007/s00216-016-9969-y International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Validation of Analytical Procedures: Text and Methodology, http://www.ich.org/products/guidelines/quality/quality-single/article/validation-of-analytical-procedures-text-and-methodology.html, 2005 (accessed 06 July 2019).