Preview

Journal of NBC Protection Corps

Advanced search

Modern Psychoactive Substances and Their Detection in Biomedical Samples

https://doi.org/10.35825/2587-5728-2022-6-4-320-341

EDN: eukkms

Abstract

Scientific and technological advancement of the mid- and late twentieth century led to the creation of a large number of new psychoactive substances (NPS), diverse in composition and spectrum of action. The primary stages of fight the spread of NPS are awareness of their characteristics, as well as the possibility of detecting both the substances themselves and biomarkers of their use (metabolites) in human biological objects. The purpose of the work is to review psychoactive compounds and methods of their detection performed for diagnostic purposes. The paper presents brief characteristics of the most common NPS, as well as features of their metabolism in the human. It is shown that the analysis of biological specimens collected from susceptive drug users is difficult due to the low content of analytes, the matrix influences, metabolism and the formation of various artifacts. The general scheme of screening of biological objects assumes the presence of two stages – a preliminary express analysis performed using immunochemical test systems, and a confirmatory analysis performed by gas and liquid chromatography-mass spectrometry. The article discusses the possibilities and limitations of targeted and non-targeted screening. The subject of special consideration was the problems of using chromatography-mass spectrometry methods of NPS analysis in Russian – issues of accessibility of standard substances, search libraries, etc. The article also presents brief characteristics of individual families of NPS, such as stimulants, synthetic cannabinoids, synthetic opioids and hallucinogens. In addition, the article shows that in a number of foreign armies, in particular, in the Armed forces of Ukraine (AFU), drugs and psychostimulants are used to create «fearless soldiers». Thus, methadone, amphetamine and other psychoactive substances, as well as a psychotomimetic – a structural and pharmacological similarity of the prohibited BZ – were found in objects delivered from the positions of the AFU for analysis.

About the Authors

A. M. Grigoryev
Federal State Budgetary Establishment «27 Scientific Centre» of the Ministry of Defence of the Russian Federation
Russian Federation

Andrej Mihajlovich Grigoryev. Research associate. Grand PhD in Chemistry.

Entuziastov passage, 19, Moscow 111024

 



V. N. Fateenkov
Federal State Budgetary Establishment «27 Scientific Centre» of the Ministry of Defence of the Russian Federation
Russian Federation

Dmitry Nikolaevich Fateenkov. Head of Department. PhD in Military Sciences, Associate Professor, Professor at the AMS.

Entuziastov passage, 19, Moscow 111024



References

1. Simonov E.A., Naydenova L.F., Vornakov S.A. Narcotic drugs and psychotropic substances controlled on the territory of the Russian Federation. Moscow: «InterLab», 2003. 413 р. (in Russian).

2. Eremin S.K., Izotov B.N., Veselovskaya N.V. Analysis of drugs. Moscow: «Mysl», 1993. 272 p. (in Russian).

3. Granik V.G. Metabolism of exogenous compounds. Moscow: «Vuzovskaya Kniga», 2015. 526 p. (in Russian).

4. Smith D., van de Waterbeemd H., Walker D.K. Pharmacokinetics and metabolism in drug design. Weinheim: Wiley-VCH Verlag GmbH, 2001. 141 p.

5. Grigoryev A.M., Krupina N.A., Nikitin E.V. et al. Study of the metabolism of the new synthetic cannabinoid MMB-022 in in vivo and in vitro models by liquid chromatography-mass spectrometry // Mass Spectrometry. 2020. V. 17. № 3. P. 151–161. (in Russian). https://doi.org/10.25703/MS.2020.17.33

6. Teske J., Weller J.P., Fieguth A. et al. Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography– tandem mass spectrometry // J. Chromatogr. B. 2010. V. 878. P. 2959–2663.

7. Grigoryev A., Savchuk S., Melnik A. et al. Chromatography–mass spectrometry studies on the metabolism of synthetic cannabinoids JWH-018 and JWH-073, psychoactive components of smoking mixtures // J. Chromatogr. B. 2011. V. 879. P. 1126.

8. Brenneisen R., Meyer P., Chtioui H. et al. Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes // Anal. Bioanal. Chem. 2010. V. 396. P. 2493–2502.

9. Grigoryev A., Kavanagh P., Labutin A. et al. Tentative identification of the metabolites of (1‐(cyclohexylmethyl)‐1H‐indol‐3‐yl)‐(2,2,3,3‐ tetramethylcyclopropyl)methanone, and the product of its thermal degradation, by in vitro and in vivo methods // Drug Test Anal. 2019. V. 11. № 9. P. 1387–1402. https://doi.org/10.1002/dta.2668

10. Temerdashev A.Z., Grigoryev A.M., Rybalchenko I.V. Narcotic drugs of natural origin and methods for their determination // J. Anal. Chem. 2016. V. 71. № 1. P. 3–22. (in Russian). https://doi.org/10.7868/S004445021601014X

11. Temerdashev A.Z., Grigoryev A.M., Rybalchenko I.V. The evolution of new drugs and methods for their determination // J. Anal. Chem. 2014. V. 69. № 9. P. 1–28. (in Russian). https://doi.org/10.7868/S0044450214090114

12. Flanagan R.J., Cuypers E., Maurer H.H., Whelpton R. Fundamentals of analytical toxicology. New York: John Wiley & Sons, Ltd, 2020. 599 p.

13. Grigoryev A.M., Rebrova S.G., Krupina N.A. Screening procedures in the analysis of objects of biological origin by liquid chromatography/mass spectrometry: possible difficulties // Narcology. 2016. № 10. P. 88–100. (in Russian).

14. Hutter M., Kneisel S., Auwärter V., Neukamm M.A. Determination of 22 synthetic cannabinoids in human hair by liquid chromatographytandem mass spectrometry // J. Chromatogr. B. 2012. V. 903. P. 95–101. https://doi.org/10.1016/j.jchromb.2012.07.002

15. Maurer H.H. Multi-analyte procedures for screening for and quantification of drugs in blood, plasma, or serum by liquid chromatography-single stage or tandem mass spectrometry (LC-MS or LC-MS/MS) relevant to clinical and forensic toxicology // Clin. Biochem. 2005. V. 38. № 4. P. 310–318. https://doi.org/10.1016/j.clinbiochem.2005.01.014

16. Kempf J., Traber J., Auwärter V., Huppertz L.M. ‘Psychotropics caught in a trap’ – adopting a screening approach to specific needs // Forensic Sci. Int. 2014. V. 243. P. 84–89. https://doi.org/10.1016/j.forsciint.2014.04.035

17. Wissenbach D.K., Meyer M.R., Remane D. et al. Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept // Anal. Bioanal. Chem. 2011. V. 40. № 10. P. 3481–3489. https://doi.org/10.1007/s00216-011-5032-1

18. Broecker S., Herre S., Pragst F. General unknown screening in hair by liquid chromatographyhybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) // Forensic Sci. Int. 2012. V. 218. № 1-3. P. 68–81. https://doi.org/10.1016/j.forsciint.2011.10.004

19. Li Z., Huang X., Wang X., Ren J., Xu B., Wang Y., Zou X., Wang L. Establishment and application of a screening method for 354 organic toxicants in blood and urine with high-performance liquid chromatographyhigh resolution orbitrap mass spectrometry // Anal. Bioanal. Chem. 2022. In press.

20. Recommended operating procedures for analysis in the verification of chemical disarmament / Ed. Vannien P. Helsinki: University of Helsinki, 2017. 809 p. http://www.helsinki.fi/veri-fin/bluebook

21. Badoud F., Grata E., Perrenoud L., Avois L. et al. Fast analysis of doping agents in urine by ultrahigh-pressure liquid chromatography–quadrupole time-of-flight mass spectrometry I. Screening analysis // J. Chromatogr. A. 2009. V. 1216. № 20. P. 4423–4433. https://doi.org/10.1016/j.chroma.2009.03.033

22. Maurer H.H. Systematic toxicological analysis of drugs and their metabolites by gas chromatographymass spectrometry // J. Chromatogr. B. 1992. V. 580. № 1-2. P. 3–41. https://doi.org/10.1016/0378-4347(92)80526-v

23. Maurer H.H. Systematic toxicological analysis procedures for acidic drugs and/or metabolites relevant to clinical and forensic toxicology and/or doping control // J. Chromatogr. B. 1999. V. 733. № 1-2. P. 3 –25. https://doi.org/10.1016/s0378-4347(99)00266-2

24. Grigoryev A., Kavanagh P., Dowling G., Rodin I. Tentative identification of etazene (etodesnitazene) metabolites in rat serum and urine by gas chromatography-mass spectrometry and accurate mass liquid chromatography-mass spectrometry // J. Anal. Toxicol. 2022. bkac001. https://doi.org/10.1093/jat/bkac001

25. Papaseit E., Moltó J., Muga R. et al. Clinical pharmacology of the synthetic cathinone mephedrone // Curr. Top. Behav. Neurosci. 2017. V. 32. P. 313–332. https://doi.org/10.1007/7854_2016_61

26. Zaikina O.L., Shilov V.V., Lodyagin A.N. et al. Establishment of the structures of free and glucuronidated metabolites of α-pyrrolidinovalerophenone in human urine by liquid chromatography-mass spectrometry when measuring accurate masses // J. Anal. Chem. 2019. V. 74. № 5. P. 381–396. https://doi.org/10.1134/S0044450219020130

27. de la Torre R., Farré M., Roset P.N. et al. Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition // Ther. Drug Monit. 2004. V. 26. № 2. P. 137–144. (in Russian). https://doi.org/10.1097/00007691-200404000-00009

28. Olesti E., Farré M., Papaseit E. et al. Pharmacokinetics of mephedrone and its metabolites in human by LC-MS/MS // AAPS J. 2017. V. 19. № 6. P. 1766–1778. https://doi.org/10.1208/s12248-017-0132-2

29. Kavanagh P., Gofenberg M., Shevyrin V. et al. Tentative identification of the phase I and II metabolites of two synthetic cathinones, MDPHP and α-PBP, in human urine // Drug Test. Anal. 2020. V. 12. № 10. P. 1442–1451. https://doi.org/10.1002/dta.2891

30. Nikitin E.V., Grigoryev A.M., Gribkova S.E. et al. Chromatography-mass spectrometric characteristics of new designer cathinones, as well as their metabolites obtained using in vivo and in vitro methods // Mass spectrometry. 2020. V. 17. № 2. P. 112–121. (in Russian). https://doi.org/10.25703/MS.2020.17.24

31. The cannabinoid receptors / Ed. Reggio P.H. New York: Humana Press, 2009. 396 p.

32. Makriyannis A., Deng H. Cannabimimetic Indole Derivatives. US Patent No. 208/0090871, 2008. 33. Гончаров Е.В., Кондрасенко А.А., Петерсон И.В. и др. Идентификация и аналитические профили синтетического каннабиноида 3,3-диметил2-(2-(1-(4-фторбензил)-1H-индол-3-ил)ацетамидо) бутанамида (ADB-FUBIATA, FUB-ACADB) // Бутлеровские сообщения. 2021. Т. 68. № 10. С. 133–140. https://doi.org/10.37952/ROI-jbc-01/21-68-10-133

33. Goncharov E.V., Kondrasenko A.A., Peterson I.V. et al. Identification and analytical profiles of the synthetic cannabinoid 3,3-dimethyl-2-(2-(1-(4-fluorobenzyl)-1Hindol-3-yl)acetamido)butanamide (ADB-FUBIATA, FUB-ACADB) // Butlerov Readings. 2021. V. 68. № 10. P. 133–140. (in Russian). https://doi.org/10.37952/ROIjbc-01/21-68-10-133

34. Liu C.-M., Hua Z.-D., Jia W., Li T. Identification of AD-18, 5F-MDA-19, and pentyl MDA-19 in seized materials after the class-wide ban of synthetic cannabinoids in China // Drug Test. Anal. 2022. V. 14. № 2. P. 307–316. https://doi.org/10.1002/dta.3185

35. Kavanagh P., Pechnikov A., Nikolaev I. et al. Detection of ADB-BUTINACA metabolites in human urine, blood, kidney and liver // J. Anal. Toxicol. 2022. V. 46. № 6. P. 641–650. https://doi.org/10.1093/jat/bkab088

36. Meyer M.R., Maurer H.H. Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse // Pharmacogenomics. 2011. V. 12. № 2. P. 215–233. https://doi.org/10.2217/pgs.10.171

37. Higashikawa Y., Suzuki S. Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) and its related compounds. VI. Structure– analgesic activity relationship for fentanyl, methylsubstituted fentanyls and other analogues // Forensic. Toxicol. 2008. V. 26. № 1. P. 1–5. https://doi.org/10.1007/s11419-007-0039-1

38. Zaikina O.L., Shilov V.V., Lodyagin A.N. et al. Features of the detection of fentanyl derivatives in urine by gas and liquid chromatography-mass spectrometry // Toxicological Bulletin. 2016. № 3. P. 41-46. (in Russian). https://doi.org/10.36946/0869-7922-2016-3-41-46

39. Rodin I.A., Gribkova S.E., Grigoryev A.M. et al. Detection of metabolites of the new psychoactive substance furanylfentanyl in the urine and blood serum of laboratory rats by liquid chromatography-mass spectrometry // Mass spectrometry. 2017. V. 14. № 4. P. 242–251. (in Russian).

40. Krotulski A.J., Papsun D.M., Kacinko S.L., Logan B.K. Isotonitazene quantitation and metabolite discovery in authentic forensic casework // J. Anal. Toxicol. 2020. V. 44. № 6. P. 521–530. https://doi.org/10.1093/jat/bkaa016

41. Braden M.R., Parrish J.C., Naylor J.C., Nichols D.E. Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists // Mol. Pharmacol. 2006. V. 70. № 6. P. 1956–1964. https://doi.org/10.1124/mol.106.028720

42. Hansen M., Phonekeo K., Paine J.S. et al. Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists // ACS Chem. Neurosci. 2014. V. 5. № 3. P. 243–249. https://doi.org/10.1021/cn400216u

43. Zaikina O.L., Shilov V.V., Lodyagin A.N. et al. Practical aspects of diagnosing the intake of compounds of the NBOMe group. Brief review of pharmacology, toxic properties and psychoactive effects // Narcology. 2018. № 9, P. 78–89. (in Russian). https://doi.org/10.25557/1682-8313.2018.09.78-89

44. Zaikina O.L., Shilov V.V., Lodyagin A.N. et al. Practical aspects of diagnosing the intake of compounds of the NBOMe group. Detection of NBOMe and their metabolites by gas and liquid chromato-mass spectrometry in biological objects // Narcology. 2018. № 10. P. 86–96. (in Russian). https://doi.org/10.25557/1682-8313.2018.10.85-96

45. Ellison D.H. Handbook of chemical and biological warfare agents. Second ed. Roca Raton, London: CRC Press, 2008.


Review

For citations:


Grigoryev A.M., Fateenkov V.N. Modern Psychoactive Substances and Their Detection in Biomedical Samples. Journal of NBC Protection Corps. 2022;6(4):320-341. (In Russ.) https://doi.org/10.35825/2587-5728-2022-6-4-320-341. EDN: eukkms

Views: 319


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2587-5728 (Print)
ISSN 3034-2791 (Online)