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IDENTIFICATION OF 4F-MDMB-BINACA METABOLITES IN HUMAN BLOOD AND URINE WITH LC-QTOF

DOI: https://doi.org/10.29296/25877313-2022-10-04
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Issue: 
10
Year: 
2022

M.A. Gofenberg
Head of Chemical-Toxicological Laboratory, Regional Narcological Clinic;
Pharmacist-Analyst, Chemical-Toxicological Laboratory, Sverdlovsk Regional Clinical Psychiatric Hospital;
Senior Lecturer, Department of Pharmacy and Chemistry, Ural State Medical University (Yekaterinburg, Russia)
E-mail: Hoffenberg@yandex.ru; ORCID: https://orcid.org/0000-0003- 2877-1301
V.A. Shevyrin
Ph.D. (Chem.), Senior Researcher, Research Laboratory for Advanced Research in the Field of Petrochemistry,
Chemical Technology and Biotechnology;
Leading Researcher Engineer, Analytical Testing Laboratory, Innovation Center for Chemical and Pharmaceutical Technologies,
Ural Federal University named after the First President of Russia B.N.Yeltsin (Yekaterinburg, Russia)
E-mail: vadim.shevyrin@gmail.com; Orcid ID: 0000-0002-0369-0786
O.N. Dvorskaya
Dr.Sc. (Pharm.), Associate Professor, Head of Department of Pharmacy and Chemistry,
Faculty of Pharmacy, South Ural State Medical University (Chelyabinsk, Russia)
E-mail: dvoksnik@gmail.com; ORCID: https://orcid.org/0000-0003-4774-8887
S.S. Kataev
Ph.D. (Chem.), Head of Forensic Chemistry Department,
Perm Regional Bureau of Forensic-Medical Expertise (Perm, Russia)
E-mail: forenschemist@narod.ru; ORCID: https://orcid.org/0000-0001-6742-2054
A.M. Grigoryev
Dr.Sc. (Chem.), Expert Chemist,
Bureau of Forensic-Medical Expertise’s, Forensic-Chemical Division (Moscow, Russia)
E-mail: chrzond4250@yandex.ru; ORCID: https://orcid.org/0000-0001-6742-2054

Relevance. Synthetic cannabinoid receptor agonists are ones of leading psychoactive substances, newly identified both in Russia and in the world. Their use is common cause of acute poisoning, sometimes fatal. As is known, synthetic cannabimimetics are intensively metabolized in human body and almost not excreted in the urine unchanged, that creates difficulties in detecting cannabinoid receptor agonists in biological material and hinders correct clinical diagnosis making. It is necessary for establishing the causes of psychoactive substances poisoning in a timely manner to explore metabolic pathways of new synthetic cannabimimetics. Aim of the work. The aim of the work is to detect of 4F-MDMB-BINACA I and II metabolite phases analysing a large number of human urine samples of the use of liquid chromatography in combination with time of flight mass spectrometry. Material and methods. We used 25 urine samples, 2 heparinized blood samples of living persons and 2 post-mortem urine samples to search for metabolites and their glucuronides 4F-MDMB-BINACA. Also we used 1290 Infinity II LC System with Zorbax Eclipse Plus C18 column for liquid chroma-tography and quadrupole time of flight LC/MS Agilent 6545 (Agilent Technologies, USA). Results. There were 49 4F-MDMB-BINACA metabolites found in human urine samples. These substances were presumably identified as hydrolyzates and hydroxylates of different fragments, defluorination with hydroxylation or carboxylation products, dihydrodiol formation derivates, N-dealkylation products and results of these reactions combination. Also were detected products of tert-leucine residue dehydrogenation, characteristics of which in-volve intramolecular cyclization with lactone formation. Main metabolic pathways were hydrolysis and defluorination, accompanied by carboxylation. Most metabolites were present in urine in free form as well as glucuronated. We have made recommendations on how metabolites and markers of new cannabimimetic could be detected using urine hydrolysis with or without sample preparation. Conclusion. Findnings of this research can be used for 4F-MDMB-BINACA acute poisoning diagnosis and to predict metabolic pathways of new synthet-ic cannabimimetics having similar structural elements.
Keywords: 
synthetic cannabimimetics
4F-MDMB-BINACA
metabolites
glucuronides
liquid chromatography Time-of-Flight mass spectrometry

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