CHARACTERISTICS OF METABOLISM AND WORKING OUT THE METHODS OF DETERMINATION OF SYNTHETIC CANNABINOID THJ-2201 IN THE URINE OF LABORATORY ANIMALS

The proposed article touches upon the study of metabolism of new synthetic cannabinoids. In the work the data on synthetic cannabinoid 3-(Naftalin-1-yloxomethyl)-1-(5-fluoropentyl)-1H-indazole (THJ-2201), as well as the products of its metabolism in the laboratory rats of the Wistar line are given, i. e. Mass spectra and chromatograms of the native substance (THJ-2201) obtained by high-performance liquid chromatography with mass-selective detection (HPLC-MS) and gas chromatography with mass-selective detection (GC-MS) are given. The paper presents a complex technique for qualitative determination of cannabimimetics THJ-2201 and methods for obtaining a metabolic profile model for the test substance that can be useful for the tasks of qualitative detection and detection of new psychoactive substances in biological objects for the purposes of forensic analysis.

The aim of this work was to develop methods for determination of the test substance (THJ-2201) and its metabolites in the urine of laboratory animals, as well as the study of the metabolic characteristics of synthetic cannabinoids on the whole.

Materials and methods. The following equipment was used for the experiment: a liquid chromatograph from the firm “Shimadzu LCMC-8050” in combination with a mass-selective detector. The detector type is a triple quadrupole with a double ionization source (chemical ionization at atmospheric pressure and electrospray). The separation of the substances occurred in a chromatographic column (the material is stainless steel, the characteristics are: 150 * 3.0 mm, Luna 3uC18 (2), 100A). The Sorbent is reversed-phase. The investigations were carried out on Agilent 7890A gas chromatograph with Agilent 5975C mass spectrometer and a 103 polar HP-5ms column of 28 m × 0.25 mm. The animals were mature male white laboratory rats of the Wistar line, aged 4–6 months, weighing 190-230 grams.

Results and discussion. As a result of the studies, a comprehensive methodology for determining the synthetic cannabimimetics of THJ-2201 and its metabolites in the urine of laboratory animals was developed, chromatograms and mass spectra of the metabolic profile of animals were obtained by HPLC-MS and GC-MS methods, and the similarity of the metabolic profiles of the studied substances in humans and animals was determined.

Conclusion. The conclusions were made about the suitability of the proposed complex analysis methodology under the given laboratory conditions and the significant degree of interspecific similarity of human metabolic profiles and laboratory rats’ for substances chemically close to the studied.

1. Federalnyj zakon ot 8 yanvarya 1998 g N3-FZ [Federal Law of January 8, 1998 N 3-FZ]. “O narkoticheskih sredstvah i psihotropnyh veshchestvah” [“On Narcotic Drugs and Psychotropic Substances”]. (In Russ.)

2. Postanovlenie Pravitelstva RF ot 30 iyunya 1998 g N 681 [Resolution of the Government of the Russian Federation of June 30, 1998 N 681] “Ob utverzhdenii perechnya narkoticheskih sredstv psihotropnyh veshchestv i ih prekursorov podlezhashchih kontrolyu v Rossijskoj Federacii” [“On the approval of the list of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation”]. (In Russ.)

3. Temerdashev A.Z., Kiseleva N.V., Kolychev I.A., Kalnitsky A.G. GH-MS I VEZHKH-MS OPREDELENIE NEKOTORYH NARKOTICHESKIH SREDSTV PRIRODNOGO I SINTETICHESKOGO PROISKHOZHDENIYA PROIZVODNYH N-ALKIL-3-INDOLILKETONOV -AMINOARILKETONOV P-AMINOBENZOJNYH KISLOT KANNABINOIDOV I TROPANOVYH ALKALOIDOV [GC-MS AND HPLC-MS DETERMINATION OF SOME DRUGS OF NATURAL AND SYNTHETIC ORIGIN DERIVATIVES OF N-ALKYL-3-INDOLYLKETONS, ɑ-AMINOARYLCRETHONES, P-AMINOBENZOIC ACIDS, CANNABINOIDS AND TROPANIC ALKALOIDS]. Analitika i control [Analytics and Control]. 2012. N 3. P. 240–247. (In Russ.)

4. Vasiliev AB, Sosnov DA, Bulygina I.E. IDENTIFIKACIYA I OSNOVNYE HARAKTERISTIKI NOVOGO SINTETICHESKOGO KANNABINOIDA NAFTALIN-1-IL 1-PENTIL-1N-INDAZOL-3-IL METANON THJ-2201 [IDENTIFICATION AND MAIN CHARACTERISTICS OF NEW SYNTHETIC CANNABINOID (NAPHTHALIN-1-IL) (1-PENTIL-1H-INDAZOL-3-IL) METHANON THJ-2201]. Nakrologiya [Nakropologiya]. 2014. No. 5 (149). P. 79–82. (In Russ.)

5. Cornelius H., Schoeder C.T., Pillaiyar T., Burkhard M., Müller C.E. PHARMACOLOGICAL EVALUATION OF SYNTHETIC CANNABINOIDS IDENTIFIED AS CONSTITUENTS OF SPICE. Forensic Toxicology. 2016. 34 (2). P. 329-343. DOI: 10.1007 / s11419-016-0320-2.

6. THJ-2201. psychonautwiki.org URL: https://psychonautwiki.org/wiki/THJ-2201.

7. METABOLIC CAGE. http://www.openscience.ru URL: http://www.openscience.ru/index.php?page=other&item=018

8. Mironov A.N. Rukovodstvo po provedeniyu doklinicheskih issledovanij lekarstvennyh sredstv [A guide to conducting preclinical studies of medicines]. Moskva: Grif i K [Мoscow: Grif and To], 2012. 751 p. (In Russ.)

9. Informacionnoe pismo “Obnaruzhenie sinteticheskih kannabimimetikov narkoticheskih psihoaktivnyh veshchestv i ih metabolitov v moche volosah i nogtyah metodami zhidkostnoj hromatografii s mass-spektrometricheskim detektirovaniem” [Information letter “Detection of synthetic cannabimimetics, narcotic, psychoactive substances and their metabolites in urine, hair and nails by liquid chromatography with mass spectrometric detection”]. Ministerstvo Zdravoohraneniya Rossijskoj Federacii Nacionalnyj nauchnyj centr narkologii [Ministry of Health of the Russian Federation, National Scientific Center of Narcology]. 2014. (In Russ.)

10. LCsolution Software. www.ssi.shimadzu.com URL: http://www.ssi.shimadzu.com/products/product.cfm?product=lcsolution.

11. Kataev S.S., Melentiev A.B., Dvorskaya O.N. IDENTIFIKACIYA METABOLITOV KANNABIMIMETIKA PB-22 V MOCHE [IDENTIFICATION OF METABOLITES OF PB-22 CANNABYMETHYME IN URINE]. Butlerovskie soobshcheniya [Butlerov Communications]. 2013. Vol. 36. No. 10. P. 29–36. (In Russ.)

12. AMDI. chemdata.nist.gov URL: http://chemdata.nist.gov/dokuwiki/doku.php?id=chemdata:amdis.

13. Apushkin D.Yu., Andreev A.I., Malkova T.L. Harakteristika metabolizma i razrabotka metodiki opredeleniya sinteticheskogo kannabinoida pb-22 v moche laboratornyh zhivotnyh [Characteristics of metabolism and development of a technique for the determination of synthetic cannabinoid pb-22 in urine of laboratory animals]. Dostizheniya i problemy sovremennoj nauki [Achievements and problems of modern science]. SPb Nauchnyj zhurnal Globus [SPb.: Scientific journal ‘’Globus’’]. 2016. P. 102–107. (In Russ.)

14. Apushkin D.Yu., Malkova T.L. Harakteristika metabolizma i razrabotka metodiki opredeleniya sinteticheskogo kannabinoida ab-pinaca v moche laboratornyh zhivotnyh [Characteristics of metabolism and working out the method of determining ab-pinaca synthetic cannabinoid in uroline of laboratory animals]. Zdorove i obrazovanie v 21 veke [Health and Education in the 21st Century]. 2016. Vol. 18. No. 10. P. 113–124. (In Russ.)