IDENTIFICATION OF CANNABIMIMETICS MDMB(N)-022 IN URINE USING SPE AND GG-MS

DOI: https://doi.org/10.29296/25877313-2022-01-02
Issue: 
1
Year: 
2022

S.S. Kataev Ph.D. (Chem.), Perm Regional Bureau of Forensic-Medical Expertise (Perm, Russia) Е-mail: forenschemist@narod.ru; https://orcid.org/0000-0001-6742-2054 O.N. Dvorskaya Dr.Sc. (Pharm.), The South Ural State Medical University (Chelyabinsk, Russia) Е-mail: dvoksnik@gmail.com; https://orcid.org/0000-0003-4774-8887 M.A. Gofenberg Senior Lecturer, Ural State Medical University; Head of Chemical-Toxicology Laboratory, Yekaterinburg State Publicly Funded Health Facility "Regional Clinical Psychiatric Hospital"; Chemist-Analyst, Chemical-Toxicology Laboratory, Sverdlovsk Regional Narcological Hospital

The relevance of research. In recent years cannabimimetic MDMB(N)-022 spreads throughout the world. Appearance of new potentially dangerous psychoactive substances makes it necessary to develop methods of their determination in biological fluids in toxicological and forensic chemistry research. Purpose of this work is to examine possibility of isolation of MDMB(N)-022 metabolites from urine, using cartridges with a mixed sorbent C8/SAX and identification of received biotransformation products by gas chromatography-mass spectrometry method. Materials and methods. During sample preparation we used enzymatic hydrolysis with β-glucuronidase (Type HP-2, From Helix Pomatia, 100000 U/ml), solid-phase extraction with a mixed sorbent C8/SAX cartridges to isolate first phase metabolites in 11 urine samples and subsequent procedure of derivatization. Recieved derivatives were examined in gas chromatograph Agilent 7820 equipped with mass-spectrometric detector Agilent 5975 (Agilent, USA).). Results. The possibility to use cartridges for SPE with a mixed sorbent C8/SAX to screening tests of urine for the presence of metabolites of cannabimimetics MDMB(N)-022 was shown. The main biotransformation directions of MDMB(N)-022 where defined. They include hydrolysis of ester bonds with following conjugation with glucuronic acid, hydrolysis of amide linkage, N-dealkylation of alkyl radical at nitrogen atom of indazole cycle, oxidative carboxylation of alkyl chain, hydroxylation and dihydrodiol metabolite formation. An analytic characteristics of main MDMB(N)-022 metabolites and their derivatives received by gas chromatography-mass spectrometry were given.

Keywords: 
synthetic cannabimimetics
MDMB(N)-022. solid-phase extraction
gas chromatography-mass spectrometry

References: 
  1. Golovko A.I., Ivnitskij Ju.Ju., Ivanov M.B., Rejnjuk V.L. Novye sinteticheskie kannabinoidy. Analiz za 2018–2020 gg. Narkologija. 2021; 1: 49–61. https://doi.org/10.25557/1682-8313.2021.01.49-61 (Golovko A.I., Ivnickij Ju.Ju., Ivanov M.B., Rejnjuk V.L. Novye sinteticheskie kannabinoidy. Analiz za 2018–2020 gg. Narkologija. 2021; 1: 49–61. https://doi.org/10.25557/1682-8313.2021.01.49-61).
  2. Krotulski A.J., Cannaert A., Stove Ch. and Logan B.K. The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues including MDMB-4en-PINACA. Drug Testing and Analysis. 2021; 13(2): 427–438. https://doi.org/10.1002/dta.2935.
  3. Norman C., Walker G., McKirdy B., McDonald C., Fletcher D., Antonides L.H., Sutcliffe O.B., Daéid N.N., McKenzie C. Detection and quantitation of synthetic cannabinoid receptor agonists in infused papers from prisons in a constantly evolving illicit market. Drug Testing and Analysis. 2020; 12(4): 538–554. https://doi.org/10.1002/dta.2767.
  4. Watanabe Sh., Vikingsson S., Åstrand A., Gréen H., Kronstrand R. Biotransformation of the New Synthetic Cannabinoid with an Alkene, MDMB-4en-PINACA, by Human Hepatocytes, Human Liver Microsomes, and Human Urine and Blood. The AAPS Journal. 2019; 22(1): 13. https://doi.org/10.1208/s12248-019-0381-3.
  5. Ozturk E.Y., Yeter O. In Vitro Phase I Metabolism of the Recently Emerged Synthetic MDMB-4en-PINACA and Its Detection in Human Urine Samples. J Anal Toxicol. 2021; 44(9): 976–984. https://doi.org/10.1093/jat/bkaa017.
  6. Cannaert A., Sparkes E., Pike E., Luo J.L., Fang A., Kevin R.C., Ellison R., Gerona R., Banister S.D., Stove Ch.P. Synthesis and in Vitro Cannabinoid Receptor 1 Activity of Recently Detected Synthetic Cannabinoids 4F-MDMB-BICA, 5F-MPP-PICA, MMB-4en-PICA, CUMYL-CBMICA, ADB-BINACA, APP-BINACA, 4F-MDMB-BINACA, MDMB-4en-PINACA, A-CHMINACA, 5F-AB-P7AICA, 5F-MDMB-P7AICA, and 5F-AP7AICA. ACS Chemical Neuroscience. 2020; 11(24): 4434–4446. https://doi.org/10.1021/acschemneuro.0c00644.
  7. O vnesenii izmenenij v nekotorye akty Pravitel'stva Ros-sijskoj Federatsii v svjazi s sovershenstvovaniem kontrolja za oborotom narkoticheskih sredstv. Postanovlenie Pravitel'-stva Ros. Federatsii ot 12.10.2015 № 1097. Rezhim dostupa: http://www.consultant.ru/document/cons_doc_LAW_ 187423/ svobodnyj (O vnesenii izmenenij v nekotorye akty Pravitel'stva Rossijskoj Federacii v svjazi s sovershenstvovaniem kontrolja za oborotom narkoticheskih sredstv. Postanov-lenie Pravitel'stva Ros. Federacii ot 12.10.2015 № 1097. Rezhim dostupa: http://www.consultant.ru/document/cons_doc_LAW_ 187423/ svobodnyj).
  8. Kataev S.S., Dvorskaja O.N., Gofenberg M.A. Identifikatsija metabolitov kannabimimetika MDMB(N)-073F v moche meto-dom gazovoj hromatografii s mass-spektro-metricheskim de-tektirovaniem. Farmatsija i farmakologija. 2019; 7(2): 4–12. https://doi.org/10.19163/2307-9266-2019-7-2-4-12 (Kataev S.S., Dvorskaja O.N., Gofenberg M.A. Identifikacija metabolitov kannabimimetika MDMB(N)-073F v moche metodom gazovoj hromatografii s mass-spektrometricheskim detektirovaniem. Farmacija i far-makologija. 2019; 7(2): 4–12. https://doi.org/10.19163/2307-9266-2019-7-2-4-12).