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Severe 25E-NBOH intoxication associated with MDPHP intake: a case report, metabolism study, and literature review

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Abstract

N-Benzylphenethylamine derivatives are 5-HT2A receptor agonists with hallucinogenic properties, including NBOMe (N-(2-methoxybenzyl)-2-(3,4,5-trimethoxyphenyl)ethan-1-amine) and NBOH (2-(((2,5-dimethoxyphenethyl)amino)methyl)phenol). We reported here the case of a 23-year-old man who presented a serotoninergic syndrome and a loss of consciousness following the consumption of a powder labelled as 25I-NBOH. Toxicological analyses of biological samples were carried out using a liquid chromatography high-resolution mass spectrometry. Two new psychoactive substances were identified and confirmed with certified reference materials: 25E-NBOH (2-(((4-ethyl-2,5-dimethoxyphenethyl)amino)methyl)phenol) and MDPHP (1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-yl)hexan-1-one). Pharmaceuticals administered to the patient during his medical care were found in plasma and urine. 25E-NBOH and MDPHP concentrations were respectively at 2.3 ng/mL and 3.4 ng/mL in plasma, and 25.7 ng/mL and 30.5 ng/mL in urine. 25I-NBOH (2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol) was specifically searched in both samples and was not detected. These results are discussed along with a literature review on human cases of exposure to N-benzylphenethylamine derivatives. Using molecular networking approach, we propose the first 25E-NBOH metabolism study using authentic biological samples (plasma and urine). We described seven metabolites (M1 to M7), including two phase I (m/z 330.172; m/z 288.160) and five phase II metabolites (m/z 464.191, m/z 478.207, m/z 492.223, m/z 508.218; m/z 396.156). The M6 (m/z 492.223) was the most intense ion detected in plasma and urine and could be proposed as a relevant 25E-NBOH consumption marker. Overall, we described an original case of 25E-NBOH poisoning and identified metabolites that could potentially be used as consumption markers to detect 25E-NBOH intoxications with a higher confidence level and probably a longer detection window.

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References

  1. Glennon RA, Dukat M, El-Bermawy M et al (1994) Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines. J Med Chem 37:1929–1935. https://doi.org/10.1021/jm00039a004

    Article  CAS  PubMed  Google Scholar 

  2. Kyriakou C, Marinelli E, Frati P et al (2015) NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review. Eur Rev Med Pharmacol Sci 19:3270–3281

    CAS  PubMed  Google Scholar 

  3. Nielsen LM, Holm NB, Leth-Petersen S et al (2017) Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I-NBOMe and 25I-NBOH: Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I-NBOMe and 25I-NBOH. Drug Test Anal 9:671–679. https://doi.org/10.1002/dta.2031

    Article  CAS  PubMed  Google Scholar 

  4. Caspar AT, Brandt SD, Stoever AE et al (2017) Metabolic fate and detectability of the new psychoactive substances 2-(4-bromo-2,5-dimethoxyphenyl)- N- [(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe) and 2-(4-chloro-2,5-dimethoxyphenyl)- N- [(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) in human and rat urine by GC–MS, LC–MS n , and LC–HR–MS/MS approaches. J Pharm Biomed Anal 134:158–169. https://doi.org/10.1016/j.jpba.2016.11.040

    Article  CAS  PubMed  Google Scholar 

  5. Grafinger KE, Stahl K, Wilke A et al (2018) In vitro phase I metabolism of three phenethylamines 25D-NBOMe, 25E-NBOMe and 25N-NBOMe using microsomal and microbial models. Drug Test Anal 10:1607–1626. https://doi.org/10.1002/dta.2446

    Article  CAS  PubMed  Google Scholar 

  6. Wang M, Carver JJ, Phelan VV et al (2016) Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol 34:828–837. https://doi.org/10.1038/nbt.3597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Allard S, Allard P-M, Morel I, Gicquel T (2018) Application of a molecular networking approach for clinical and forensic toxicology exemplified in three cases involving 3-MeO-PCP, doxylamine, and chlormequat. Drug Test Anal. https://doi.org/10.1002/dta.2550

  8. Le Daré B, Allard S, Bouvet R et al (2020) A case of fatal acebutolol poisoning: an illustration of the potential of molecular networking. Int J Legal Med 134:251–256. https://doi.org/10.1007/s00414-019-02062-9

    Article  PubMed  Google Scholar 

  9. Pelletier R, Le Daré B, Grandin L et al (2021) New psychoactive substance cocktail in an intensive care intoxication case elucidated by molecular networking. Clin Toxicol Phila Pa 1–4. https://doi.org/10.1080/15563650.2021.1931693

  10. Allard S, Allard P-M, Morel I, Gicquel T (2019) Application of a molecular networking approach for clinical and forensic toxicology exemplified in three cases involving 3-MeO-PCP, doxylamine, and chlormequat. Drug Test Anal 11:669–677. https://doi.org/10.1002/dta.2550

    Article  CAS  PubMed  Google Scholar 

  11. Le Daré B, Ferron P-J, Allard P-M et al (2020) New insights into quetiapine metabolism using molecular networking. Sci Rep 10:19921. https://doi.org/10.1038/s41598-020-77106-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Le Daré B, Ferron P-J, Couette A et al (2021) In vivo and in vitro α-amanitin metabolism studies using molecular networking. Toxicol Lett 346:1–6. https://doi.org/10.1016/j.toxlet.2021.04.006

    Article  CAS  PubMed  Google Scholar 

  13. Kernalléguen A, Le Daré B, Pelletier R et al (2022) Carbofuran self-poisoning: forensic and analytic investigations in twins and literature review. Int J Legal Med 136:1585–1596. https://doi.org/10.1007/s00414-022-02885-z

    Article  PubMed  Google Scholar 

  14. Pelletier R, Le Daré B, Ferron P-J et al (2022) Use of innovative, cross-disciplinary in vitro, in silico and in vivo approaches to characterize the metabolism of chloro-alpha-pyrrolidinovalerophenone (4-Cl-PVP). Arch Toxicol. https://doi.org/10.1007/s00204-022-03427-7

  15. Pluskal T, Castillo S, Villar-Briones A, Oresic M (2010) MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics 11:395. https://doi.org/10.1186/1471-2105-11-395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. https://doi.org/10.1101/gr.1239303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Grapp M, Kaufmann C, Schwelm HM et al (2020) Intoxication cases associated with the novel designer drug 3’,4’-methylenedioxy-α-pyrrolidinohexanophenone and studies on its human metabolism using high-resolution mass spectrometry. Drug Test Anal 12:1320–1335. https://doi.org/10.1002/dta.2869

    Article  CAS  PubMed  Google Scholar 

  18. Kavanagh P, Gofenberg M, Shevyrin V et al (2020) Tentative identification of the phase I and II metabolites of two synthetic cathinones, MDPHP and α-PBP, in human urine. Drug Test Anal 12:1442–1451. https://doi.org/10.1002/dta.2891

    Article  CAS  PubMed  Google Scholar 

  19. Di Candia D, Boracchi M, Ciprandi B et al (2022) A unique case of death by MDPHP with no other co-ingestion: a forensic toxicology case. Int J Legal Med. https://doi.org/10.1007/s00414-022-02799-w

  20. Hieger MA, Rose SR, Cumpston KL et al (2015) Severe poisoning after self-reported use of 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, a novel substituted amphetamine: a case series. Am J Emerg Med 33:1843.e1–1843.e3. https://doi.org/10.1016/j.ajem.2015.04.065

    Article  CAS  PubMed  Google Scholar 

  21. Poklis JL, Devers KG, Arbefeville EF et al (2014) Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. Forensic Sci Int 234:e14–e20. https://doi.org/10.1016/j.forsciint.2013.10.015

    Article  CAS  PubMed  Google Scholar 

  22. Lowe LM, Peterson BL, Couper FJ (2015) A case review of the first analytically confirmed 25I-NBOMe-related death in Washington State. J Anal Toxicol 39:668–671. https://doi.org/10.1093/jat/bkv092

    Article  CAS  PubMed  Google Scholar 

  23. Shanks KG, Sozio T, Behonick GS (2015) Fatal intoxications with 25B-NBOMe and 25I-NBOMe in Indiana During 2014. J Anal Toxicol 39:602–606. https://doi.org/10.1093/jat/bkv058

    Article  CAS  PubMed  Google Scholar 

  24. Kueppers VB, Cooke CT (2015) 25I-NBOMe related death in Australia: a case report. Forensic Sci Int 249:e15–e18. https://doi.org/10.1016/j.forsciint.2015.02.010

    Article  CAS  PubMed  Google Scholar 

  25. Suzuki J, Poklis JL, Poklis A (2014) “My friend said it was good LSD”: a suicide attempt following analytically confirmed 25I-NBOMe ingestion. J Psychoactive Drugs 46:379–382. https://doi.org/10.1080/02791072.2014.960111

    Article  PubMed  PubMed Central  Google Scholar 

  26. Poklis JL, Nanco CR, Troendle MM et al (2014) Determination of 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe) in serum and urine by high performance liquid chromatography with tandem mass spectrometry in a case of severe intoxication. Drug Test Anal 6:764–769. https://doi.org/10.1002/dta.1522

    Article  CAS  PubMed  Google Scholar 

  27. Isbister GK, Poklis A, Poklis JL, Grice J (2015) Beware of blotting paper hallucinogens: severe toxicity with NBOMes. Med J Aust 203:266-267e.1. https://doi.org/10.5694/mja15.00650

    Article  Google Scholar 

  28. Yoshida K-I, Saka K, Shintani-Ishida K et al (2015) A case of fatal intoxication due to the new designer drug 25B-NBOMe. Forensic Toxicol 33. https://doi.org/10.1007/s11419-015-0276-7

  29. Laskowski LK, Elbakoush F, Calvo J et al (2015) Evolution of the NBOMes: 25C- and 25B- Sold as 25I-NBOMe. J Med Toxicol Off J Am Coll Med Toxicol 11:237–241. https://doi.org/10.1007/s13181-014-0445-9

    Article  Google Scholar 

  30. Gee P, Schep LJ, Jensen BP et al (2016) Case series: toxicity from 25B-NBOMe—a cluster of N-bomb cases. Clin Toxicol Phila Pa 54:141–146. https://doi.org/10.3109/15563650.2015.1115056

    Article  Google Scholar 

  31. de Souza AC, Sardela VF, de Sousa VP, Pereira HMG (2018) Zebrafish ( Danio rerio ): A valuable tool for predicting the metabolism of xenobiotics in humans? Comp Biochem Physiol Part C Toxicol Pharmacol 212:34–46. https://doi.org/10.1016/j.cbpc.2018.06.005

    Article  CAS  Google Scholar 

  32. Richter LHJ, Herrmann J, Andreas A et al (2019) Tools for studying the metabolism of new psychoactive substances for toxicological screening purposes — a comparative study using pooled human liver S9, HepaRG cells, and zebrafish larvae. Toxicol Lett 305:73–80. https://doi.org/10.1016/j.toxlet.2019.01.010

    Article  CAS  PubMed  Google Scholar 

  33. Hugbart C, Verres Y, Le Daré B et al (2020) Non-oxidative ethanol metabolism in human hepatic cells in vitro: involvement of uridine diphospho-glucuronosyltransferase 1A9 in ethylglucuronide production. Toxicol In Vitro 66:104842. https://doi.org/10.1016/j.tiv.2020.104842

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. INSERM, INRAE, CHU Rennes, Institut NuMeCan (Nutrition, Metabolism and Cancer), PREVITOX Network, F-35033, Rennes, France

    Romain Pelletier, Thomas Gicquel, Isabelle Morel & Brendan Le Daré

  2. Rennes University Hospital, Clinical and Forensic Toxicology Laboratory, F-35033, Rennes, France

    Romain Pelletier, Thomas Gicquel & Isabelle Morel

  3. AP-HM, DepaICMrtment of Intensive Care, Réanimation des Urgences, Medicine Intensive & Reanimation, Timone University Hospital, Marseille, France

    Julien Carvelli

  4. Bataillon des Marins Pompiers, Groupement Santé, Service Médical d’Urgence, 9 Boulevard de Strasbourg, 13233, Marseille Cedex 20, France

    Pierre Balaz

  5. Aix Marseille Univ, APHM, INSERM, INMED UMR 901, La Timone University Hospital, Legal Medicine Department, 13005, Marseille, France

    Anne-Laure Pelissier-Alicot

  6. LAT LUMTOX Laboratory, Lyon, France

    Charline Bottinelli

  7. Laboratory of Pharmacokinetics and Toxicology, La Timone University Hospital, 264 rue Saint Pierre, 13385, Marseille Cedex 5, France

    Caroline Solas & Nicolas Fabresse

  8. Rennes University Hospital, Pharmacy department, F-35033, Rennes, France

    Brendan Le Daré

  9. Aix Marseille University, INSERM, IRD, SESSTIM, Economic and Social Sciences of Health and Medical Information Processing, Marseille, France

    Nicolas Fabresse

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  1. Romain Pelletier
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Contributions

Conceptualization: NF, RP, TG, CB; methodology: NF, RP, TG, CB; formal analysis and investigation: all authors; writing — original draft preparation: NF, RP, TG, BLD; writing — review and editing: all authors; supervision: NF, TG.

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Correspondence to Romain Pelletier.

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Ethical approval was waived in view of the retrospective nature of the study, and all the procedures being performed were part of the routine care.

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Pelletier, R., Gicquel, T., Carvelli, J. et al. Severe 25E-NBOH intoxication associated with MDPHP intake: a case report, metabolism study, and literature review. Int J Legal Med 138, 815–822 (2024). https://doi.org/10.1007/s00414-023-03151-6

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