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Blood concentrations of new synthetic opioids

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Abstract

Purpose

Over the last decade, there has been a significant growth in the market and number of new psychoactive substances (NPS). One of the NPS groups that has grown rapidly in recent years, bringing a new set of problems, consists of new synthetic opioids. The extreme potency of these compounds poses a high risk of acute poisoning, as an overdose can cause respiratory depression. Most of the information regarding human pharmacokinetics of new opioids is based on toxicological case reports and the data on concentrations of new opioids in human blood are scarce. The interpretation of results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful.

Methods

The data were collected by searching the PubMed and Scopus databases and by using the Google search engine. All the available data from articles and reports that measured new opioid concentrations in plasma, serum, or whole blood were included in the data analysis.

Results

The presented tables list the observed concentrations in fatal and nonfatal cases involving 37 novel synthetic opioids.

Conclusions

Blood levels of new opioids are extremely difficult to interpret. Low blood concentrations of these substances do not rule out acute poisoning as their high potency creates a risk of respiratory depression even at low doses. Opioid tolerance, frequent presence of other drugs, and additional diseases make it impossible to define concentration ranges, especially the minimum fatal concentrations. This report provides quick access to the source articles quantifying novel synthetic opioids.

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References

  1. Lovrecic B, Lovrecic M, Gabrovec B, Carli M, Pacini M, Maremmani A, Maremmani I (2019) Non-medical use of novel synthetic opioids: a new challenge to public health. Int J Environ Res Public Health 16(2):177. https://doi.org/10.3390/ijerph16020177

    Article  CAS  PubMed Central  Google Scholar 

  2. European Monitoring Centre for Drugs and Drug Addiction (2020) New psychoactive substances: global markets, global threats and the COVID-19 pandemic. Publications office of the European Union, Luxembourg, An update from the EU Early Warning System. https://doi.org/10.2810/921262

    Book  Google Scholar 

  3. European Monitoring Centre for Drugs and Drug Addiction (2020) European drug report 2020: trends and developments. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/420678

    Article  Google Scholar 

  4. Seth P, Scholl L, Rudd RA, Bacon S (2018) Overdose deaths involving opioids, cocaine, and psychostimulants-United States 2015–2016. MMWR Morb Mortal Wkly Rep 67:349–358. https://doi.org/10.15585/mmwr.mm6712a1

    Article  PubMed  PubMed Central  Google Scholar 

  5. United Nations Office on Drugs and Crime, World Drug Report 2017 (ISBN: 978–92–1–148291–1, eISBN: 978–92–1–060623–3, United Nations publication, Sales No. E.17.XI.6).

  6. Helland A, Brede WR, Michelsen LS, Gundersen POM, Aarset H, Skjølås JE, Slørdal L (2017) Two hospitalizations and one death after exposure to ortho-fluorofentanyl. J Anal Toxicol 41:708–709. https://doi.org/10.1093/jat/bkx050

    Article  CAS  PubMed  Google Scholar 

  7. Sofalvi S, Schueler HE, Lavins ES, Kaspar CK, Brooker IT, Mazzola CD, Dolinak D, Gilson TP, Perch S (2017) An LC-MS-MS method for the analysis of carfentanil, 3-methylfentanyl, 2-furanyl fentanyl, acetyl fentanyl, fentanyl and norfentanyl in postmortem and impaired-driving cases. J Anal Toxicol 41:473–483. https://doi.org/10.1093/jat/bkx052

    Article  CAS  PubMed  Google Scholar 

  8. Sofalvi S, Lavins ES, Brooker IT, Kaspar CK, Kucmanic J, Mazzola CD, Mitchell-Mata CL, Clyde CL, Rico RN, Apollonio LG, Goggin C, Marshall B, Moore D, Gilson TP (2019) Unique structural/stereo-isomer and isobar analysis of novel fentanyl analogues in postmortem and DUID whole blood by UHPLC-MS-MS. J Anal Toxicol 43:673–687. https://doi.org/10.1093/jat/bkz056

    Article  CAS  PubMed  Google Scholar 

  9. Müller D, Neurath H, Neukamm MA, Wilde M, Despicht C, Blaschke S, Grapp M (2019) New synthetic opioid cyclopropylfentanyl together with other novel synthetic opioids in respiratory insufficient comatose patients detected by toxicological analysis. Clin Toxicol 57:806–812. https://doi.org/10.1080/15563650.2018.1554187

    Article  CAS  Google Scholar 

  10. Helander A, Bäckberg M, Signell P, Beck O (2017) Intoxications involving acrylfentanyl and other novel designer fentanyls - results from the Swedish STRIDA project. Clin Toxicol 55:589–599. https://doi.org/10.1080/15563650.2017.1303141

    Article  CAS  Google Scholar 

  11. Bäckberg M, Beck O, Jönsson KH, Helander A (2015) Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project. Clin Toxicol 53:609–617. https://doi.org/10.3109/15563650.2015.1054505

    Article  CAS  Google Scholar 

  12. Pardi J, Toriello A, Cooper G (2020) Evaluation of 4-fluoroisobutyrylfentanyl in blood samples from 247 authentic cases submitted to the New York City Office of Chief Medical Examiner in 2017–2018. Forensic Toxicol 30:340–351. https://doi.org/10.1007/s11419-019-00518-6

    Article  CAS  Google Scholar 

  13. Helander A, Bäckberg M, Beck O (2016) Intoxications involving the fentanyl analogs acetylfentanyl, 4-methoxybutyrfentanyl and furanylfentanyl: results from the Swedish STRIDA project. Clin Toxicol 54:324–332. https://doi.org/10.3109/15563650.2016.1139715

    Article  CAS  Google Scholar 

  14. United Nations Office on Drugs and Crime (2018) Recommended methods for the identification and analysis of fentanyl and its analogues in biological specimens. Manual for use by national drug analysis laboratories. https://doi.org/10.18356/aca7aca5-en.

  15. Ujváry I, Jorge R, Christie R, Le Ruez T, Danielsson HV, Kronstrand R, Elliott S, Gallegos A, Sedefov R, Evans-Brown M (2017) Acryloylfentanyl, a recently emerged new psychoactive substance: a comprehensive review. Forensic Toxicol 35:232–243. https://doi.org/10.1007/s11419-017-0367-8

    Article  CAS  Google Scholar 

  16. Bernius A, Blaas V, Rentsch D, Büttner A, Thome J (2016) Unerwartete Komplikationen während des Entzugs vom Research Chemical AH-7921. Fortschr Neurol Psychiatr 84:80–83. https://doi.org/10.1055/s-0042-113960

    Article  Google Scholar 

  17. Hendrickson RG, Akpunonu P, Hughes AR, Gerona R (2019) Highly potent fentanyl analogs: apnea from exposure to small quantities of ß-hydroxyfentanyl and furanylfentanyl. Clin Toxicol 57:813–815. https://doi.org/10.1080/15563650.2018.1558233

    Article  CAS  Google Scholar 

  18. Verougstraete N, Vandeputte MM, Lyphout C, Cannaert A, Hulpia F, Van Calenbergh S, Verstraete AG, Stove C (2021) First report on Brorphine: the next opioid on the deadly new psychoactive substance horizon? J Anal Toxicol 44:937–946. https://doi.org/10.1093/jat/bkaa094

    Article  CAS  PubMed  Google Scholar 

  19. Chan WS, Wong GF, Hung CW, Wong YN, Fung KM, Lee WK, Dao KL, Leung CW, Lo KM, Lee WM, Cheung BK (2020) Interpol review of toxicology 2016–2019. Forensic Sci Int Synerg 23:563–607. https://doi.org/10.1016/j.fsisyn.2020.01.018(openaccessarticle)

    Article  Google Scholar 

  20. Allibe N, Fouilhe Sam-Lai N, Willeman T, Jourdil JF, Bartoli M, Mallaret M, Nemoz B, Stanke-Labesque F, Eysseric-Guerin H (2019) Norcarfentanil: carfentanil misuse or remifentanil treatment? Forensic Toxicol 37:488–495. https://doi.org/10.1007/s11419-019-00481-2(openaccessarticle)

    Article  CAS  Google Scholar 

  21. Müller S, Nussbaumer S, Plitzko G, Ludwig R, Weinmann W, Krähenbühl S, Liakoni E (2017) Recreational use of carfentanil - a case report with laboratory confirmation. Clin Toxicol 56:151–152. https://doi.org/10.1080/15563650.2017.1355464

    Article  Google Scholar 

  22. Uddayasankar U, Lee C, Oleschuk C, Eschun G, Ariano RE (2018) The pharmacokinetics and pharmacodynamics of carfentanil after recreational exposure: a case report. Pharmacotherapy 38:e41–e45. https://doi.org/10.1002/phar.2117

    Article  PubMed  Google Scholar 

  23. Brunetti P, Pirani F, Carlier J, Giorgetti R, Busardò FP, Lo Faro AF (2020) A 2017-2019 update on acute intoxications and fatalities from illicit fentanyl and analogues. J Anal Toxicol 45(6):537–554. https://doi.org/10.1093/jat/bkaa115

    Article  Google Scholar 

  24. Leen JLS, Juurlink DN (2019) Carfentanil: a narrative review of its pharmacology and public health concerns. Can J Anaesth 66:414–421. https://doi.org/10.1007/s12630-019-01294-y

    Article  CAS  PubMed  Google Scholar 

  25. Lelièvre B, Abbara C, Benatre H, Férec S, Bretaudeau M, Gegu C, Bruneau C, Boels D, Harry P, Turcant A, Diquet B (2014) Deux cas d’intoxication par le T61®. Toxicologie Toxicol Anal et Clin 27:203–210. https://doi.org/10.1016/j.toxac.2015.04.001

    Article  Google Scholar 

  26. Hartman RL, Salomone ME, Nemeth DJ, Gallagher TM, Fellows JS, Kadlec LM, Beno JM (2017) Furanyl fentanyl, butyryl fentanyl, and U-47700 in blood and urine of drivers arrested for driving under the influence of drugs (DUID). [S171] Presented at Society of Forensic Toxicologist (SOFT) Meeting in Boca Raton. http://www.soft-tox.org/files/meeting_abstracts/SOFT_2017_meeting_abstracts.pdf. Accessed 27 May 2021

  27. Helander A, Bäckberg M, Beck O (2014) MT-45, a new psychoactive substance associated with hearing loss and unconsciousness. Clin Toxicol 52:901–904. https://doi.org/10.3109/15563650.2014.943908

    Article  CAS  Google Scholar 

  28. Helander A, Bradley M, Hasselblad A, Norlén L, Vassilaki I, Bäckberg M, Lapins J (2017) Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45. Br J Dermatol 176:1021–1027. https://doi.org/10.1111/bjd.15174

    Article  CAS  PubMed  Google Scholar 

  29. Baumann MH, Tocco G, Papsun DM, Mohr AL, Fogarty MF, Krotulski AJ (2020) U-47700 and its analogs: non-fentanyl synthetic opioids impacting the recreational drug market. Brain Sci 10:895. https://doi.org/10.3390/brainsci10110895(openaccessarticle)

    Article  CAS  PubMed Central  Google Scholar 

  30. Sharma KK, Hales TG, Rao VJ, NicDaeid N, McKenzie C (2019) The search for the “next” euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning. Forensic Toxicol 37:1–16. https://doi.org/10.1007/s11419-018-0454-5(openaccessarticle)

    Article  CAS  PubMed  Google Scholar 

  31. Armenian P, Olson A, Anaya A, Kurtz A, Ruegner R, Gerona RR (2017) Fentanyl and a novel synthetic opioid U-47700 masquerading as street “Norco” in central California: a case report. Ann Emerg Med 69:87–90. https://doi.org/10.1016/j.annemergmed.2016.06.014

    Article  PubMed  Google Scholar 

  32. Židková M, Horsley R, Hloch O, Hložek T (2019) Near-fatal intoxication with the “new” synthetic opioid U-47700: the first reported case in the Czech Republic. J Forensic Sci 64:647–650. https://doi.org/10.1111/1556-4029.13903

    Article  CAS  PubMed  Google Scholar 

  33. Vogliardi S, Stocchero G, Maietti S, Tucci M, Nalesso A, Snenghi R, Favretto D (2018) Non-fatal overdose with U-47700: identification in biological matrices. Curr Pharm Biotechnol 19:180–187. https://doi.org/10.2174/1389201019666180509164240

    Article  CAS  PubMed  Google Scholar 

  34. Jones MJ, Hernandez BS, Janis GC, Stellpflug SJ (2017) A case of U-47700 overdose with laboratory confirmation and metabolite identification. Clin Toxicol 55:55–59. https://doi.org/10.1080/15563650.2016.1209767

    Article  Google Scholar 

  35. Vo KT, van Wijk XM, Wu AH, Lynch KL, Ho RY (2017) Synthetic agents off the darknet: a case of U-47700 and phenazepam abuse. Clin Toxicol 55:71–72. https://doi.org/10.1080/15563650.2016.1240806

    Article  Google Scholar 

  36. Chapman BP, Lai JT, Krotulski AJ, Fogarty MF, Griswold MK, Logan BK, Babu KM (2019) A case of unintentional opioid (U-47700) overdose in a young adult after counterfeit Xanax use. Pediatr Emerg Care 37(9):e579–e580. https://doi.org/10.1097/PEC.0000000000001775

    Article  Google Scholar 

  37. Andreasen MF, Hardlei TF, Rosendal I, Thomsen AH, Johannsen M, Sædder E (2017) A fatal poisoning involving 2-fluorofentanyl. [P5] Presented at Society of Forensic Toxicologist (SOFT) Meeting in Boca Raton. http://www.soft-tox.org/files/meeting_abstracts/SOFT_2017_meeting_abstracts.pdf. Accessed 27 May 2021

  38. Moody MT, Diaz S, Shah P, Papsun D, Logan BK (2018) Analysis of fentanyl analogs and novel synthetic opioids in blood, serum/plasma, and urine in forensic casework. Drug Test Anal 10:1358–1367. https://doi.org/10.1002/dta.2393

    Article  CAS  PubMed  Google Scholar 

  39. Salle S, Bodeau S, Dhersin A, Ferdonnet M, Goncalves R, Lenski M, Lima B, Martin M, Outreville J, Vaucel J, Fabress N (2019) Novel synthetic opioids: a review of the literature. Toxicol Anal et Clin 31:298–316. https://doi.org/10.1016/j.toxac.2019.10.001

    Article  Google Scholar 

  40. Giorgetti A, Centola C, Giorgetti R (2017) Fentanyl novel derivative-related deaths. Hum Psychopharmacol 32:e2605. https://doi.org/10.1002/hup.2605

    Article  CAS  Google Scholar 

  41. Concheiro M, Chesser R, Pardi J, Cooper G (2018) Postmortem toxicology of New Synthetic Opioids. Front Pharmacol 26:1210. https://doi.org/10.3389/fphar.2018.01210

    Article  CAS  Google Scholar 

  42. Schueler HE (2017) Emerging synthetic fentanyl analogs. Acad Forensic Pathol 7:36–40. https://doi.org/10.23907/2017.004

    Article  PubMed  PubMed Central  Google Scholar 

  43. Frisoni P, Bacchio E, Bilel S, Talarico A, Gaudio RM, Barbieri M, Neri M, Marti M (2018) Novel Synthetic Opioids: the pathologist’s point of view. Brain Sci 2:170. https://doi.org/10.3390/brainsci8090170(openaccessarticle)

    Article  Google Scholar 

  44. Friscia M, Papsun D, Logan BK (2017) Deaths related to abuse of 3-methylfentanyl in the United States. [S22] Presented at Society of Forensic Toxicologist (SOFT) Meeting in Boca Raton. http://www.soft-tox.org/files/meeting_abstracts/SOFT_2017_meeting_abstracts.pdf. Accessed 27 May 2021

  45. Ojanperä I, Gergov M, Rasanen I, Lunetta P, Toivonen S, Tiainen E, Vuori E (2006) Blood levels of 3-methylfentanyl in 3 fatal poisoning cases. Am J Forensic Med Pathol 27:328–331. https://doi.org/10.1097/01.paf.0000188097

    Article  PubMed  Google Scholar 

  46. Fogarty MF, Papsun DM, Logan BK (2018) Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high resolution mass spectrometry and findings in forensic toxicology casework. Drug Test Anal 10:1474–1482. https://doi.org/10.1002/dta.2414

    Article  CAS  PubMed  Google Scholar 

  47. Ojanperä I, Gergov M, Liiv M, Riikoja A, Vuori E (2008) An epidemic of fatal 3-methylfentanyl poisoning in Estonia. Int J Legal Med 122:395–400. https://doi.org/10.1007/s00414-008-0230-x

    Article  PubMed  Google Scholar 

  48. Drummer OH (2018) Fatalities caused by novel opioids: a review. Forensic Sci Res 4:95–110. https://doi.org/10.1080/20961790.2018.1460063(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  49. Yong HL, Harper CE, Frost K (2017) Non-pharmaceutical fentanyls encountered by the Alabama Department of Forensic Sciences (ADFS) [P32] Presented at Society of Forensic Toxicologist (SOFT) Meeting in Boca Raton. http://www.soft-tox.org/files/meeting_abstracts/SOFT_2017_meeting_abstracts.pdf. Accessed 27 May 2021

  50. Fogarty MF, Mohr ALA, Papsun DM, Logan BK (2020) Analysis of the illicit opioid U-48800 and related compounds by LC-MS/MS and case series of fatalities involving U-48800. J Anal Toxicol 25:bkaa180. https://doi.org/10.1093/jat/bkaa180

    Article  Google Scholar 

  51. Garneau B, Desharnais B, Beauchamp-Doré A, Lavallée C, Mireault P, Lajeunesse A (2020) Challenges related to three cases of fatal intoxication to multiple novel synthetic opioids. J Anal Toxicol 44:86–91. https://doi.org/10.1093/jat/bkz018

    Article  CAS  PubMed  Google Scholar 

  52. Danaceau J, Wood M, Ehlers M, Rosano T (2020) Analysis of 17 fentanyls in plasma and blood by UPLC-MS/MS with interpretation of findings in surgical and postmortem casework. Clin Mass Spectrom 18:38–47. https://doi.org/10.1016/j.clinms.2020.10.003

    Article  PubMed  PubMed Central  Google Scholar 

  53. Busardò FP, Carlier J, Giorgetti R, Tagliabracci A, Pacifici R, Gottardi M, Pichini S (2019) Ultra-high-performance liquid chromatography-tandem mass spectrometry assay for quantifying fentanyl and 22 analogs and metabolites in whole blood, urine, and hair. Front Chem 7:184. https://doi.org/10.3389/fchem.2019.00184(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  54. Martucci HFH, Ingle EA, Hunter MD, Rodda LN (2017) Distribution of furanyl fentanyl and 4-ANPP in an accidental acute death: a case report. Forensic Sci Int 283:e13–e17. https://doi.org/10.1016/j.forsciint.2017.12.005

    Article  CAS  PubMed  Google Scholar 

  55. Chesser R, Pardi J, Concheiro M, Cooper G (2019) Distribution of synthetic opioids in postmortem blood, vitreous humor and brain. Forensic Sci Int 305:109999. https://doi.org/10.1016/j.forsciint.2019.109999

    Article  CAS  PubMed  Google Scholar 

  56. Freni F, Pezzella S, Vignali C, Moretti M, Cisini S, Rossetti C, Ravizza R, Motta M, Groppi A, Morini L (2019) A case report on potential postmortem redistribution of furanyl fentanyl and 4-ANPP. Forensic Sci Int 304:109915. https://doi.org/10.1016/j.forsciint.2019.109915

    Article  CAS  PubMed  Google Scholar 

  57. Lee J, Krotulski AJ, Fogarty MF, Papsun DM, Logan BK (2019) Chromatographic separation of the isobaric compounds cyclopropylfentanyl, crotonylfentanyl, methacrylfentanyl, and para-methylacrylfentanyl for specific confirmation by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 1118–1119:164–170. https://doi.org/10.1016/j.jchromb.2019.04.033

    Article  CAS  PubMed  Google Scholar 

  58. European Monitoring Centre for Drugs and Drug Addiction. Furanylfentanyl Report on the risk assessment of N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide (furanylfentanyl) in the framework of the Council Decision on new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/716236

  59. Rojkiewicz M, Majchrzak M, Celiński R, Kuś P, Sajewicz M (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 9:405–414. https://doi.org/10.1002/dta.2135

    Article  CAS  PubMed  Google Scholar 

  60. Zawilska JB (2017) An expanding world of Novel Psychoactive Substances: Opioids. Front Psychiatry 8:110. https://doi.org/10.3389/fpsyt.2017.00110(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ad LE, Alzghari SK (2020) Systematic review of the clinical consequences of butyrfentanyl and corresponding analogues. Interdiscip Toxicol 12:83–88. https://doi.org/10.2478/intox-2019-0009(openaccessarticle)

    Article  Google Scholar 

  62. Strehmel N, Vejmelka E, Kastner K, Roscher S, Tsokos M, Scholtis S (2017) NPS-findings in forensic toxicology – three case reports. Toxichem Krimtech 84:199–204

    Google Scholar 

  63. Fogarty MF, Papsun DM, Logan BK (2018) Analysis of fentanyl and 18 novel fentanyl analogs and metabolites by LC-MS-MS, and report of fatalities associated with methoxyacetylfentanyl and cyclopropylfentanyl. J Anal Toxicol 42:592–604. https://doi.org/10.1093/jat/bky035

    Article  CAS  PubMed  Google Scholar 

  64. Adamowicz P, Bakhmut Z, Mikolajczyk A (2020) Screening procedure for 38 fentanyl analogues and five other new opioids in whole blood by liquid chromatography-tandem mass spectrometry. J Appl Toxicol 40:1033–1046. https://doi.org/10.1002/jat.3962

    Article  CAS  PubMed  Google Scholar 

  65. European Monitoring Centre for Drugs and Drug Addiction. 4F-iBF Report on the risk assessment of N-(4-fluorophenyl)-2-methyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide in the framework of the Council Decision on new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/64132

  66. Kahl JH, Gonyea J, Humphrey SM, Hime GW, Boland DM (2018) Quantitative analysis of fentanyl and six fentanyl analogs in postmortem specimens by UHPLC-MS-MS. J Anal Toxicol 42:570–580. https://doi.org/10.1093/jat/bky054

    Article  CAS  PubMed  Google Scholar 

  67. Kraemer M, Boehmer A, Madea B, Maas A (2019) Death cases involving certain new psychoactive substances: A review of the literature. Forensic Sci Int 298:186–267. https://doi.org/10.1016/j.forsciint.2019.02.021

    Article  CAS  PubMed  Google Scholar 

  68. Guerrieri D, Kjellqvist F, Kronstrand R, Gréen H (2019) Validation and cross-reactivity data for fentanyl analogs with the immunalysis fentanyl ELISA. J Anal Toxicol 43:18–24. https://doi.org/10.1093/jat/bky060

    Article  CAS  PubMed  Google Scholar 

  69. Papsun DM, Chan-Hosokawa A, Friederich L, Brower J, Graf K, Logan B (2019) The trouble with kratom: analytical and interpretative issues involving mitragynine. J Anal Toxicol 43:615–629. https://doi.org/10.1093/jat/bkz064

    Article  CAS  PubMed  Google Scholar 

  70. Zawadzki M, Wachełko O, Chłopaś-Konowałek A, Szpot P (2021) Quantification and distribution of 4-fluoroisobutyryl fentanyl (4-FiBF) in postmortem biological samples using UHPLC-QqQ-MS/MS. Forensic Toxicol. https://doi.org/10.1007/s11419-021-00584-9 [ahead of print]

  71. Kacinko S (2016) Detecting designer opioids and benzodiazepines: understanding the options. Workshop #5 Toxicology of Designer Benzodiazepines and Opioids. Presented at Society of Forensic Toxicologist (SOFT) Meeting in Dallas. http://soft-tox.org/files/annual_meeting/Workshops/W5ToxDesigner1.pdf. Accessed 27 May 2021

  72. Mata D (2016) Clinical and postmortem findings in cases related to designer benzodiazepines and opioids. Workshop #5 Toxicology of Designer Benzodiazepines and Opioids. Presented at Society of Forensic Toxicologist (SOFT) Meeting in Dallas. http://soft-tox.org/files/annual_meeting/Workshops/W5ToxDesigner1.pdf. Accessed 27 May 2021

  73. McIntyre IM, Trochta A, Gary RD, Malamatos M, Lucas JR (2015) An acute acetyl fentanyl fatality: a case report with postmortem concentrations. J Anal Toxicol 39:490–494. https://doi.org/10.1093/jat/bkv043

    Article  CAS  PubMed  Google Scholar 

  74. McIntyre IM, Trochta A, Gary RD, Wright J, Mena O (2016) An acute butyr-fentanyl fatality: a case report with postmortem concentrations. J Anal Toxicol 40:162–166. https://doi.org/10.1093/jat/bkv138

    Article  CAS  PubMed  Google Scholar 

  75. Cunningham SM, Haikal NA, Kraner JC (2016) Fatal intoxication with acetyl fentanyl. J Forensic Sci Suppl 1:S276-280. https://doi.org/10.1111/1556-4029.12953

    Article  Google Scholar 

  76. Takase I, Koizumi T, Fujimoto I, Yanai A, Fujimiya T (2016) An autopsy case of acetyl fentanyl intoxication caused by insufflation of ‘designer drugs.’ Leg Med 21:38–44. https://doi.org/10.1016/j.legalmed.2016.05.006

    Article  CAS  Google Scholar 

  77. Yonemitsu K, Sasao A, Mishima S, Ohtsu Y, Nishitani Y (2016) A fatal poisoning case by intravenous injection of “bath salts” containing acetyl fentanyl and 4-methoxy PV8. Forensic Sci Int 267:e6–e9. https://doi.org/10.1016/j.forsciint.2016.08.025

    Article  CAS  PubMed  Google Scholar 

  78. Fort C, Curtis B, Nichols C, Niblo C (2016) Acetyl fentanyl toxicity: two case reports. J Anal Toxicol 40:754–757. https://doi.org/10.1093/jat/bkw068

    Article  CAS  PubMed  Google Scholar 

  79. Pearson J, Poklis J, Poklis A, Wolf C, Mainland M, Hair L, Devers K, Chrostowski L, Arbefeville E, Merves M (2015) Postmortem toxicology findings of acetyl fentanyl, fentanyl, and morphine in heroin fatalities in Tampa, Florida. Acad Forensic Pathol 5:676–689. https://doi.org/10.23907/2015.072

    Article  PubMed  Google Scholar 

  80. Dwyer JB, Janssen J, Luckasevic TM, Williams KE (2018) Report of increasing overdose deaths that include acetyl fentanyl in multiple counties of the southwestern region of the Commonwealth of Pennsylvania in 2015–2016. J Forensic Sci 63:195–200. https://doi.org/10.1111/1556-4029.13517

    Article  CAS  PubMed  Google Scholar 

  81. Knittel JL, Jackson GF, Gordon CJ, Walterscheid JP (2017) Distribution and stability of acetyl fentanyl and acetyl norfentanyl in a heroin related death. [S185] Presented at Society of Forensic Toxicologist (SOFT) Meeting in Boca Raton. http://www.soft-tox.org/files/meeting_abstracts/SOFT_2017_meeting_abstracts.pdf. Accessed 27 May 2021

  82. Fagiola M, Hahn T, Avella J (2019) Evaluation of acetylfentanyl following suspected heroin overdose when complicated by the presence of toxic fentanyl and alprazolam concentrations. [P01] Presented at Society of Forensic Toxicologist (SOFT) Meeting in San Antonio. http://soft-tox.org/files/2019_meeting/PosterAbstracts.pdf. Accessed 27 May 2021

  83. Katselou M, Papoutsis J, Nikolaou P, Spiliopoulou C, Athanaselis S (2016) Old opioids, new concerns: the case of acetylfentanyl. Forensic Toxicol 34:201–212. https://doi.org/10.1007/s11419-016-0310-4

    Article  CAS  Google Scholar 

  84. Avedschmidt S, Schmidt C, Isenschmid D, Kesha K, Moons D, Gupta A (2018) Acetyl fentanyl: trends and concentrations in Metro Detroit. J Forensic Sci 64:149–153. https://doi.org/10.1111/1556-4029.13840

    Article  CAS  PubMed  Google Scholar 

  85. Finkelstein MJ, Chronister CW, Stanley C, Ogilvie LM, Goldberger BA (2019) Analysis of acetyl fentanyl in postmortem specimens by gas chromatography-mass spectrometry (GC-MS): method validation and case report. J Anal Toxicol 43:392–398. https://doi.org/10.1093/jat/bky108

    Article  CAS  PubMed  Google Scholar 

  86. Poklis J, Poklis A, Wolf C, Mainland M, Hair L, Devers K, Chrostowski L, Arbefeville E, Merves M, Pearson J (2015) Postmortem tissue distribution of acetyl fentanyl, fentanyl and their respective nor-metabolites analyzed by ultrahigh performance liquid chromatography with tandem mass spectrometry. Forensic Sci Int 257:435–441. https://doi.org/10.1016/j.forsciint.2015.10.021(openaccessarticle)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mills K, Huston B, Froloff V, McGee M (2019) Acetyl Fentanyl: acute toxicity case report. J Forensic Sci Toxicol. 2:1006 (open access article)

  88. World Health Organization (2015) Acetylfentanyl Critical Review Report Agenda item 5.2. Expert Committee of Drug Dependence Thirty-seventh meeting. Geneva. https://www.who.int/medicines/access/controlled-substances/5.2_Acetylfentanyl_CRev.pdf. Accessed 27 May 2021

  89. Moss DM, Brown DH, Douglas BJ (2017) An acetyl fentanyl death in Western Australia. Aust J Forensic Sci 51:73–77. https://doi.org/10.1080/00450618.2017.1315836

    Article  Google Scholar 

  90. Guerrieri D, Rapp E, Roman M, Thelander G, Kronstrand R (2017) Acrylfentanyl: another new psychoactive drug with fatal consequences. Forensic Sci Int 277:e21–e29. https://doi.org/10.1016/j.forsciint.2017.05.010

    Article  CAS  PubMed  Google Scholar 

  91. Butler DC, Shanks K, Behonick GS, Smith D, Presnell SE, Tormos LM (2018) Three cases of fatal acrylfentanyl toxicity in the United States and a review of literature. J Anal Toxicol 42:e6–e11. https://doi.org/10.1093/jat/bkx083

    Article  CAS  PubMed  Google Scholar 

  92. Gerace E, Salomone A, Vincenti M (2018) Analytical approaches in fatal intoxication cases involving new synthetic opioids. Curr Pharm Biotechnol 19:113–123. https://doi.org/10.2174/1389201019666180405162734(openaccessarticle)

    Article  CAS  PubMed  Google Scholar 

  93. Kronstrand R, Thelander G, Lindstedt D, Roman M, Kugelberg FC (2014) Fatal intoxications associated with the designer opioid AH-7921. J Anal Toxicol 38:599–604. https://doi.org/10.1093/jat/bku057

    Article  CAS  PubMed  Google Scholar 

  94. Vorce SP, Knittel JL, Holler JM, Magluilo J Jr, Levine B, Berran P, Bosy TZ (2014) A fatality involving AH-7921. J Anal Toxicol 38:226–230. https://doi.org/10.1093/jat/bku011

    Article  CAS  PubMed  Google Scholar 

  95. Karinen R, Tuv SS, Rogde S, Peres MD, Johansen U, Frost J, Vindenes V, Øiestad ÅM (2014) Lethal poisonings with AH-7921 in combination with other substances. Forensic Sci Int 244:e21–e24. https://doi.org/10.1016/j.forsciint.2014.08.013

    Article  CAS  PubMed  Google Scholar 

  96. World Health Organization (2014) AH-7921Critical Review Report Agenda item 4.21. Expert Committee of Drug Dependence Thirty-sixth meeting. Geneva. https://www.who.int/medicines/areas/quality_safety/4_21_review.pdf. Accessed 27 May 2021

  97. Fels H, Krueger J, Sachs H, Musshoff F, Graw M, Roider G, Stoever A (2017) Two fatalities associated with synthetic opioids: AH-7921 and MT-45. Forensic Sci Int 277:e30–e35. https://doi.org/10.1016/j.forsciint.2017.04.003

    Article  CAS  PubMed  Google Scholar 

  98. Coppola M, Mondola R (2017) From potential analgesic medicine to recreational drug. Int J High Risk Behav Addict 6:e22593. https://doi.org/10.5812/ijhrba.22593

    Article  Google Scholar 

  99. Gillespie TJ, Gandolfi AJ, Davis TP, Morano RA (1982) Identification and quantification of alpha-methylfentanyl in post mortem specimens. J Anal Toxicol 6:139–142. https://doi.org/10.1093/jat/6.3.139

    Article  CAS  PubMed  Google Scholar 

  100. Baselt RC. (2017) Disposition of Toxic Drugs and Chemicals in Man. 11th edition, Biomedical Publications, Seal Beach, CA. ISBN 978-0-692-77499-1

  101. Krotulski AJ, Papsun DM, Noble C, Kacinko SL, Logan BK (2021) Brorphine-Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry. J Forensic Sci 66:664–676. https://doi.org/10.1111/1556-4029.14623

    Article  CAS  PubMed  Google Scholar 

  102. Vohra V, King AM, Jacobs E, Aaron C (2021) Death associated with brorphine, an emerging novel synthetic opioid. Clin Toxicol 1:1–4. https://doi.org/10.1080/15563650.2021.1879111. [ahead of print]

  103. Poklis J, Poklis A, Wolf C, Hathaway C, Arbefeville E, Chrostowski L, Devers K, Hair L, Mainland M, Merves M, Pearson J (2016) Two fatal intoxications involving butyryl fentanyl. J Anal Toxicol 40:703–708. https://doi.org/10.1093/jat/bkw048(openaccessarticle)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Staeheli SN, Baumgartner MR, Gauthier S, Gascho D, Jarmer J, Kraemer T, Steuer AE (2016) Time-dependent postmortem redistribution of butyrfentanyl and its metabolites in blood and alternative matrices in a case of butyrfentanyl intoxication. Forensic Sci Int 266:170–177. https://doi.org/10.1016/j.forsciint.2016.05.034

    Article  CAS  PubMed  Google Scholar 

  105. Swanson DM, Hair LS, Strauch Rivers SR, Smyth BC, Brogan SC, Ventoso AD, Vaccaro SL, Pearson JM (2017) Fatalities involving carfentanil and furanyl fentanyl: two case reports. J Anal Toxicol 41:498–502. https://doi.org/10.1093/jat/bkx037

    Article  CAS  PubMed  Google Scholar 

  106. Hikin L, Smith PR, Ringland E, Hudson S, Morley SR (2018) Multiple fatalities in the North of England associated with synthetic fentanyl analogue exposure: detection and quantitation a case series from early 2017. Forensic Sci Int 282:179–183. https://doi.org/10.1016/j.forsciint.2017.11.036

    Article  CAS  PubMed  Google Scholar 

  107. Papsun D, Isenschmid D, Logan BK (2017) Observed carfentanil concentrations in 355 blood specimens from forensic investigations. J Anal Toxicol 41:777–778. https://doi.org/10.1093/jat/bkx068

    Article  CAS  PubMed  Google Scholar 

  108. Shanks KG, Behonick GS (2017) Detection of carfentanil by LC-MS-MS and reports of associated fatalities in the USA. J Anal Toxicol 41:466–472. https://doi.org/10.1093/jat/bkx042

    Article  CAS  PubMed  Google Scholar 

  109. Elliott SP, Hernandez Lopez E (2018) A series of deaths involving carfentanil in the UK and associated post-mortem blood concentrations. J Anal Toxicol 42:e41–e45. https://doi.org/10.1093/jat/bkx109

    Article  CAS  PubMed  Google Scholar 

  110. Cannaert A, Ambach L, Blanckaert P, Stove CP (2018) Activity-based detection and bioanalytical confirmation of a fatal carfentanil intoxication. Front Pharmacol 9:486. https://doi.org/10.3389/fphar.2018.00486(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  111. Gaulier JM, Richeval C, Phanithavong M, Brault S, Allorge D, Dumestre-Toulet V (2019) A case report of carfentanil-related fatality in France. Toxicol Anal et Clin 31:323–331. https://doi.org/10.1016/j.toxac.2019.01.002

    Article  Google Scholar 

  112. Chan WS, Wong GF, Lee WM (2021) Carfentanil related death first encountered in Hong Kong: two case report. Forensic Sci Int 2021:100181. https://doi.org/10.1016/j.fsir.2021.100181(openaccessarticle)

    Article  Google Scholar 

  113. Chatterton CN, Handy RP, Shoemaker GK, Scott-Ham M (2020) The distribution and redistribution of carfentanil in post mortem samples. Forensic Sci Int 309:110215. https://doi.org/10.1016/j.forsciint.2020.110215

    Article  CAS  PubMed  Google Scholar 

  114. Corsi NJ, Dragovic LJ (2019) Fatal overdoses involving carfentanil: a case series. J Forensic Sci Med 5:147–150. https://doi.org/10.4103/jfsm.jfsm_74_17

    Article  Google Scholar 

  115. Rab E, Flanagan RJ, Hudson S (2019) Detection of fentanyl and fentanyl analogues in biological samples using liquid chromatography-high resolution mass spectrometry. Forensic Sci Int 300:13–18. https://doi.org/10.1016/j.forsciint.2019.04.008

    Article  CAS  PubMed  Google Scholar 

  116. Fomin D, Baranauskaite V, Usaviciene E, Sumkovskaja A, Laima S, Jasulaitis A, Minkuviene ZN, Chmieliauskas S, Stasiuniene J (2018) Human deaths from drug overdoses with carfentanyl involvement-new rising problem in forensic medicine: a STROBE-compliant retrospective study. Medicine 97:e13449. https://doi.org/10.1097/MD.0000000000013449(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  117. Wilcoxon RM, Middleton OL, Meyers SE, Kloss J, Love SA (2018) The elephant in the room: outbreak of carfentanil deaths in Minnesota and the importance of multiagency collaboration. Acad Forensic Pathol 8:729–737. https://doi.org/10.1177/1925362118797746(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  118. European Monitoring Centre for Drugs and Drug Addiction (2018) Carfentanil Report on the risk assessment of methyl 1-(2-phenylethyl)-4-[phenyl(propanoyl)amino]piperidine-4-carboxylate in the framework of the Council Decision on new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/411341

    Article  Google Scholar 

  119. Misailidi N, Papoutsis I, Nikolaou P, Dona A, Spiliopoulou C, Athanaselis S (2018) Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil. Forensic Toxicol 36:12–32. https://doi.org/10.1007/s11419-017-0379-4(openaccessarticle)

    Article  CAS  PubMed  Google Scholar 

  120. Zawilska JB, Kuczyńska K, Kosmal W, Markiewicz K, Adamowicz P (2021) Carfentanil - from an animal anesthetic to a deadly illicit drug. Forensic Sci Int 320:110715. https://doi.org/10.1016/j.forsciint.2021.110715

    Article  CAS  PubMed  Google Scholar 

  121. Fagiola M, Hahn T, Avella J (2019) Five postmortem case reports with qualitative analysis of cyclopropylfentanyl by LC-MS-MS. J Anal Toxicol 43:e1–e6. https://doi.org/10.1093/jat/bky094

    Article  CAS  PubMed  Google Scholar 

  122. Brockbals L, Staeheli SN, Gentile S, Schlaepfer M, Bissig C, Bolliger SA, Kraemer T, Steuer AE (2019) Fatal poisoning involving cyclopropylfentanyl - investigation of time-dependent postmortem redistribution. Forensic Sci Int 294:80–85. https://doi.org/10.1016/j.forsciint.2018.11.007

    Article  CAS  PubMed  Google Scholar 

  123. European Monitoring Centre for Drugs and Drug Addiction (2018) Cyclopropylfentanyl Report on the risk assessment of N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]cyclopropanecarboxamide in the framework of the Council Decision on new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/895612

    Article  Google Scholar 

  124. Castellino C, Van Cleve D, Cabrera R (2021) Two cyclopropyl fentanyl case studies in Los Angeles. J Anal Toxicol 45:105–109. https://doi.org/10.1093/jat/bkaa037

    Article  CAS  PubMed  Google Scholar 

  125. Matey JM, García-Ruíz C, Montalvo G, Gómez-Soro JC, Gutierrez-Delicado D, Rodríguez-Gallardo J, Martínez MA (2020) Ultraviolet-visible and high-resolution mass spectrometry for the identification of cyclopropyl-fentanyl in the first fatal case in Spain. J Anal Toxicol 44:927–935. https://doi.org/10.1093/jat/bkaa081

    Article  CAS  PubMed  Google Scholar 

  126. Morini L, Pozzi F, Risso E, Vignali C, Groppi A (2012) Distribution of embutramide and mebezonium iodide in a suicide after tanax injection. J Anal Toxicol 36:349–352. https://doi.org/10.1093/jat/bks030

    Article  CAS  PubMed  Google Scholar 

  127. Kintz P, Cirimele V, Ludes B (2002) Blood investigation in a fatality involving the veterinary drug T-61. J Anal Toxicol 26:529–531. https://doi.org/10.1093/jat/26.7.529

    Article  CAS  PubMed  Google Scholar 

  128. Abe E, Delamoye M, Mathieu B, Durigon M, de Mazancourt P, Advenier C, Alvarez JC (2004) A rapid and sensitive high-performance liquid chromatography method for determination of embutramide (a Tanax or T61 component) in human blood with photodiode-array UV detection. J Anal Toxicol 28:118–121. https://doi.org/10.1093/jat/28.2.118

    Article  CAS  PubMed  Google Scholar 

  129. Musshoff F, Kirschbaum KM, Madea B (2013) Another suicide using the veterinary drug T61 and distribution of drugs in the body. J Anal Toxicol 37:186. https://doi.org/10.1093/jat/bks140

    Article  CAS  PubMed  Google Scholar 

  130. Guareschi EE, Maker GL, Tobe SS (2019) Murder-Suicide by Tanax® - pathology, toxicology and veterinary analysis of a forensic case. Glob J of Forensic Sci & Med 2:GJFSM.MS.ID.000529. https://doi.org/10.33552/GJFSM.2019.02.000529

  131. Mohr AL, Friscia M, Papsun D, Kacinko SL, Buzby D, Logan BK (2016) Analysis of novel synthetic opioids U-47700, U-50488 and furanyl fentanyl by LC-MS/MS in postmortem casework. J Anal Toxicol 40:709–717. https://doi.org/10.1093/jat/bkw086

    Article  CAS  PubMed  Google Scholar 

  132. Guerrieri D, Rapp E, Roman M, Druid H, Kronstrand R (2017) Postmortem and toxicological findings in a series of furanylfentanyl-related deaths. J Anal Toxicol 41:242–249. https://doi.org/10.1093/jat/bkw129

    Article  CAS  PubMed  Google Scholar 

  133. Milroy CM, Kepron C (2017) Two deaths associated with Furanylfentanyl toxicity. Forensic Sci Int IAFS special issue:88.

  134. Papsun D, Hawes A, Mohr ALA, Friscia M, Logan BK (2017) Case series of novel illicit opioid-related deaths. Acad Forensic Pathol 7:477–486. https://doi.org/10.23907/2017.040 (open access article)

  135. European Monitoring Centre for Drugs and Drug Addiction (2017) Furanylfentanyl Report on the risk assessment of N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]furan-2-carboxamide (furanylfentanyl) in the framework of the Council Decision on new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/716236

    Article  Google Scholar 

  136. Dybowski MP, Dawidowicz AL (2020) Furanylfentanyl in whole blood measured by GC-MS/MS after QuEChERS extraction in a fatal case. Forensic Toxicol 38:496–504. https://doi.org/10.1007/s11419-019-00515-9

    Article  Google Scholar 

  137. Nash C, Butzbach D, Stockham P, Scott T, Abroe G, Painter B, Gilbert J, Kostakis C (2019) A fatality involving furanylfentanyl and MMMP, with presumptive identification of three MMMP metabolites in urine. J Anal Toxicol 43:291–298. https://doi.org/10.1093/jat/bky099

    Article  CAS  PubMed  Google Scholar 

  138. Strayer KE, Antonides HM, Juhascik MP, Daniulaityte R, Sizemore IE (2018) LC-MS/MS-based method for the multiplex detection of 24 fentanyl analogues and metabolites in whole blood at sub ng mL-1 concentrations. ACS Omega 3:514–523. https://doi.org/10.1021/acsomega.7b01536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Vandeputte MM, Cannaert A, Stove CP (2020) In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances. Arch Toxicol 94:3819–3830. https://doi.org/10.1007/s00204-020-02855-7

    Article  CAS  PubMed  Google Scholar 

  140. Krotulski AJ, Papsun DM, Kacinko SL, Logan BK (2020) Isotonitazene quantitation and metabolite discovery in authentic forensic casework. J Anal Toxicol 44:521–530. https://doi.org/10.1093/jat/bkaa016

    Article  CAS  PubMed  Google Scholar 

  141. Mueller F, Bogdal C, Pfeiffer B, Andrello L, Ceschi A, Thomas A, Grata E (2021) Isotonitazene: fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland. Forensic Sci Int 320:110686. https://doi.org/10.1016/j.forsciint.2021.110686(openaccessarticle)

    Article  CAS  PubMed  Google Scholar 

  142. World Health Organization (2020) Critical Review Report: ISOTONITAZENE Expert Committee on Drug Dependence Forty-third meeting. Geneva. https://www.who.int/docs/default-source/controlled-substances/43rd-ecdd/isonitazene-43rd-final-complete-a.pdf?sfvrsn=c98d9c9_2 Accessed 27 May 2021

  143. European Monitoring Centre for Drugs and Drug Addiction (2018) Methoxyacetylfentanyl Report on the risk assessment of 2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide in the framework of the Council Decision on new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/520464

    Article  Google Scholar 

  144. Mardal M, Johansen SS, Davidsen AB, Telving R, Jornil JR, Dalsgaard PW, Hasselstrøm JB, Øiestad ÅM, Linnet K, Andreasen MF (2018) Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and in vitro metabolite profiling in pooled human hepatocytes. Forensic Sci Int 290:310–317. https://doi.org/10.1016/j.forsciint.2018.07.020

    Article  CAS  PubMed  Google Scholar 

  145. Andreasen MF, Telving R, Øiestad ÅML, Bergh MS, Rosendal I, Jornil JR, Larsen MK, Nielsen TA, Hasselstrøm JB (2018) Methoxyacetylfentanyl in two fatal poisonings and identification of the in vivo main metabolites. [P098] Presented at The International Association of Forensic Toxicologists (TIAFT) Meeting. Ghent, Belgium, 26–30.08.2018.

  146. European Monitoring Centre for Drugs and Drug Addiction (2015) MT-45 Report on the risk assessment of MT-45 in the framework of the Council Decisionon new psychoactive substances. Publications office of the European Union, Luxembourg. https://doi.org/10.2810/59253

    Article  Google Scholar 

  147. Papsun D, Krywanczyk A, Vose JC, Bundock EA, Logan BK (2016) Analysis of MT-45, a novel synthetic opioid, in human whole blood by LC-MS-MS and its identification in a drug-related death. J Anal Toxicol 40:313–317. https://doi.org/10.1093/jat/bkw012

    Article  CAS  PubMed  Google Scholar 

  148. World Health Organization (2020) MT-45 Critical Review Report Agenda item 5.1 Expert Committee on Drug Dependence Thirty-seventh meeting. Geneva. https://www.who.int/medicines/access/controlled-substances/5.1_MT-45_CRev.pdf. Accessed 27 May 2021

  149. Coopman V, Cordonnier J, De Leeuw M, Cirimele V (2016) Ocfentanil overdose fatality in the recreational drug scene. Forensic Sci Int 266:469–473. https://doi.org/10.1016/j.forsciint.2016.07.005

    Article  CAS  PubMed  Google Scholar 

  150. Dussy FE, Hangartner S, Hamberg C, Berchtold C, Scherer U, Schlotterbeck G, Wyler D, Briellmann TA (2016) An acute ocfentanil fatality: a case report with postmortem concentrations. J Anal Toxicol 40:761–766. https://doi.org/10.1093/jat/bkw096

    Article  CAS  PubMed  Google Scholar 

  151. Allibe N, Richeval C, Phanithavong M, Faure A, Allorge D, Paysant F, Stanke-Labesque F, Eysseric-Guerin H, Gaulier JM (2018) Fatality involving ocfentanil documented by identification of metabolites. Drug Test Anal 10:995–1000. https://doi.org/10.1002/dta.2326

    Article  CAS  PubMed  Google Scholar 

  152. Casati S, Minoli M, Angeli I, Ravelli A, Crudele GDL, Orioli M (2019) An ocfentanil-related death case: UHPLC-MS/MS analysis of the drug. Drug Test Anal 11:173–177. https://doi.org/10.1002/dta.2473

    Article  CAS  PubMed  Google Scholar 

  153. Allibe N, Billault F, Moreau C, Marchard A, Gaillard Y, Hoizey G, Eysseric-Guerin H, Milan N (2019) Ocfentanil in France: seven case reports (2016–2018). Toxicol Anal et Clin 31:317–322. https://doi.org/10.1016/j.toxac.2018.12.003

    Article  Google Scholar 

  154. Briellman T, Dussy F, Hantgartner S, Wyler D (2016) An intoxication with ocfentanil. [V-030] 95. Jahrestagung der Deutchen Gesellschaft für Rechtsmedizin. Heidelberg Rechtsmedizin 26:340–410. https://doi.org/10.1007/s00194-016-0109-y

    Article  Google Scholar 

  155. Kronstrand R, Roman M, Thelander G, Eriksson A (2011) Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 35:242–247. https://doi.org/10.1093/anatox/35.4.242

    Article  CAS  PubMed  Google Scholar 

  156. Krotulski AJ, Papsun DM, Friscia M, Swartz JL, Holsey BD, Logan BK (2018) Fatality following ingestion of tetrahydrofuranylfentanyl, U-49900 and methoxy-phencyclidine. J Anal Toxicol 42:e27–e32. https://doi.org/10.1093/jat/bkx092

    Article  CAS  PubMed  Google Scholar 

  157. Elliott SP, Brandt SD, Smith C (2016) 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. Drug Test Anal 8:875–879. https://doi.org/10.1002/dta.1984

    Article  CAS  PubMed  Google Scholar 

  158. Coopman V, Blanckaert P, Van Parys G, Van Calenbergh S, Cordonnier J (2016) A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700). Forensic Sci Int 266:68–72. https://doi.org/10.1016/j.forsciint.2016.05.001

    Article  CAS  PubMed  Google Scholar 

  159. Dziadosz M, Klintschar M, Teske J (2017) Postmortem concentration distribution in fatal cases involving the synthetic opioid U-47700. Int J Legal Med 131:1555–1556. https://doi.org/10.1007/s00414-017-1593-7

    Article  PubMed  Google Scholar 

  160. Ellefsen KN, Taylor EA, Simmons P, Willoughby V, Hall BJ (2017) Multiple drug-toxicity involving novel psychoactive substances, 3-fluorophenmetrazine and U-47700. J Anal Toxicol 41:765–770. https://doi.org/10.1093/jat/bkx060

    Article  CAS  PubMed  Google Scholar 

  161. McIntyre IM, Gary RD, Joseph S, Stabley R (2017) A fatality related to the synthetic opioid U-47700: postmortem concentration distribution. J Anal Toxicol 41:158–160. https://doi.org/10.1093/jat/bkw124

    Article  CAS  PubMed  Google Scholar 

  162. Rohrig TP, Miller SA, Baird TR (2018) U-47700: a not so new opioid. J Anal Toxicol 42:e12–e14. https://doi.org/10.1093/jat/bkx081

    Article  CAS  PubMed  Google Scholar 

  163. Gerace E, Salomone A, Luciano C, Di Corcia D, Vincenti M (2018) First case in Italy of fatal intoxication involving the new opioid U-47700. Front Pharmacol 9:747. https://doi.org/10.3389/fphar.2018.00747(openaccessarticle)

    Article  PubMed  PubMed Central  Google Scholar 

  164. Koch K, Auwärter V, Hermanns-Clausen M, Wilde M, Neukamm MA (2018) Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine flubromazepam with lethal outcome: pharmacokinetic data. Drug Test Anal https://doi.org/10.1002/dta.2391 [ahead of print]

  165. Fels H, Lottner-Nau S, Sax T, Roider G, Graw M, Auwärter V, Musshoff F (2019) Postmortem concentrations of the synthetic opioid U-47700 in 26 fatalities associated with the drug. Forensic Sci Int 301:e20–e28. https://doi.org/10.1016/j.forsciint.2019.04.010

    Article  CAS  PubMed  Google Scholar 

  166. Lowry J, Truver MT, Swortwood MJ (2019) Quantification of seven novel synthetic opioids in blood using LC-MS/MS. Forensic Toxicol 37:215–223. https://doi.org/10.1007/s11419-018-0458-1

    Article  CAS  Google Scholar 

  167. Partridge E, Trobbiani S, Stockham P, Charlwood C, Kostakis C (2018) A case study involving U-47700, diclazepam and flubromazepam-application of retrospective analysis of HRMS data. J Anal Toxicol 42:655–660. https://doi.org/10.1093/jat/bky039

    Article  CAS  PubMed  Google Scholar 

  168. Nikolaou P, Katselou M, Papoutsis I, Spiliopoulou C, Anthanselis S (2017) U-47700. An old opioid becomes a recent danger. Forensic Toxicol 35:11–19. https://doi.org/10.1007/s11419-016-0347-4

    Article  CAS  Google Scholar 

  169. Nowak K, Szpot P, Zawadzki M (2021) Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences. Forensic Toxicol. https://doi.org/10.1007/s11419-020-00568-1 [ahead of print] (open access article)

  170. Kriikku P, Pelander A, Rasanen I, Ojanperä I (2019) Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by re-analysis of UPLC-TOF-MS data. Forensic Sci Int 300:85–88. https://doi.org/10.1016/j.forsciint.2019.04.030

    Article  CAS  PubMed  Google Scholar 

  171. Richeval C, Gaulier JM, Romeuf L, Allorge D, Gaillard Y (2019) Case report: relevance of metabolite identification to detect new synthetic opioid intoxications illustrated by U-47700. Int J Legal Med 133:133–142. https://doi.org/10.1007/s00414-018-1969-3

    Article  PubMed  Google Scholar 

  172. Rojek S, Romańczuk A, Kula K, Synowiec K, Kłys M (2019) 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–ESI-MS-MS. Forensic Toxicol 37:339–349. https://doi.org/10.1007/s11419-019-00464-3

    Article  CAS  Google Scholar 

  173. Smith CR, Truver MT, Swortwood MJ (2019) Quantification of U-47700 and its metabolites in plasma by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 1112:41–47. https://doi.org/10.1016/j.jchromb.2019.02.026

    Article  CAS  PubMed  Google Scholar 

  174. Strehmel N, Dümpelmann D, Vejmelka E, Strehmel V, Roscher S, Scholtis S, Tsokos M (2018) Another fatal case related to the recreational abuse of U-47700. Forensic Sci Med Pathol 14:531–535. https://doi.org/10.1007/s12024-018-0018-3

    Article  CAS  PubMed  Google Scholar 

  175. Walsh EE, Shoff EN, Elizabeth Zaney M, Hime GW, Garavan F, Boland DM (2019) To test or not to test?: the value of toxicology in a delayed overdose death. J Forensic Sci 64:314–317. https://doi.org/10.1111/1556-4029.13822

    Article  PubMed  Google Scholar 

  176. Aiello L, Skwarek E, Isenschmidt D, Dragovic LJ (2020) U-47700 – Incidence of a novel psychoactive substance in a series of medical examiner cases in Oakland County. MI J Forensic Sci Med 6:105–109. https://doi.org/10.4103/jfsm.jfsm_2_20

    Article  Google Scholar 

  177. Ruan X, Chiravuri S, Kaye AD (2016) Comparing fatal cases involving U-47700. Forensic Sci Med Pathol 12:369–371. https://doi.org/10.1007/s12024-016-9795-8

    Article  PubMed  Google Scholar 

  178. Kegler R, Port A, Büttner A, Rentsch D (2019) Intoxication with the new opioid U-47700 – a case report in the northeast of Germany. [P08] Presented at 21. Mosbacher Symposium. Mosbach, Germany, 11–13.04.2019.

  179. Adamowicz P (2020) Blood concentrations of synthetic cathinones. Clin Toxicol. https://doi.org/10.1080/15563650.2020.1848100 [ahead of print]

  180. Adamowicz P (2021) Blood concentrations of synthetic cannabinoids. Clin Toxicol 59:246–251. https://doi.org/10.1080/15563650.2020.1787429

    Article  CAS  Google Scholar 

  181. Nowak K, Adamowicz P (2021) Blood concentrations of new psychoactive substances belonging to benzodiazepine class. Forensic Toxicol. https://doi.org/10.1007/s11419-021-00581-y [ahead of print]

  182. Jung BF, Reidenberg MM (2005) Interpretation of opioid levels: comparison of levels during chronic pain therapy to levels from forensic autopsies. Clin Pharmacol Ther 77:324–334. https://doi.org/10.1016/j.clpt.2004.10.013

    Article  CAS  PubMed  Google Scholar 

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  1. Institute of Forensic Research, Westerplatte 9, 31-033, Krakow, Poland

    Piotr Adamowicz

  2. Institute of Toxicology Research, Kasztanowa 45, 55-093, Borowa, Poland

    Karolina Nowak

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Adamowicz, P., Nowak, K. Blood concentrations of new synthetic opioids. Int J Legal Med 136, 107–122 (2022). https://doi.org/10.1007/s00414-021-02729-2

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