SYNTHETIC CATHINONES: STRUCTURE, TOXICODYNAMICS, TOXICOKINETICS, TOXICOLOGICAL ANALYSIS
DOI:
https://doi.org/10.11603/2312-0967.2023.2.14052Keywords:
psychotropic substances, synthetic cathinones, α-PVP, mephedrone, MDPV, TLCAbstract
The aim of the work. To conduct a critical analysis of scientific information regarding the need to study toxicological properties, toxicokinetics and detection methods of synthetic cathinones.
Materials and Methods. To conduct a comprehensive scientific study, the authors used online databases: PubMed and Google Scholar, as well as information from the web pages of government agencies involved in the control and identification systems of the compounds under investigation: the United Nations Office on Drugs and Crime (UNODC); the European Monitoring Center for Drugs and Drug Addiction (EMCDDA); World Health Organization (WHO); National Forensic Laboratory Information System (NFLIS); Drug Enforcement Administration (DEA) programs; EMCDDA Early Warning Systems (EWS).
Results and Discussion. According to the results of the review of literature data, the substances under consideration (cathinones) are one of the components of the general toxicological stress faced by modern people in Ukraine. The wide distribution of drug poisonings, which were not encountered before, presents certain difficulties for doctors related to clinical and laboratory diagnosis, as well as to the treatment of patients and medical examination for the state of drug intoxication. A sharp increase in the number of poisonings, including fatal ones, where cathinones occupy a significant place among others, increases the importance of detecting these substances.
Conclusions. Most of the illicitly developed synthetic cathinones can be considered analogues manufactured to replace controlled compounds, the use of which has decreased as a result of legislative measures. They may become more widespread in the future and may pose a significant threat to human health and life. That is why it is so important to develop methods of analytical toxicology of new compounds.
References
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report. 2016: Trends and Developments, Publications Office of the European Union, Luxembourg; 2016. 84 p.
Report of the International Narcotics Control Board for 2014. International Narcotics Control Board. United Nations. New York; 2015. 126 p.
Understanding the synthetic drug market: the NPS factor. UNODC, Global SMART Update. Vol. 19. UNODC Research; 2018. 12 р.
Petyunin GP, Chubenko OV, Dmitrievskaya ZhV. Methodology for the identification of amphetamine, its synthetic derivatives and homemade analogues. Theory and practice of forensic examination and criminology. 2002; 2: 335-8.
On approval of the list of narcotic drugs, psychotropic substances and precursors. Resolution of the Cabinet of Ministers of Ukraine № 770, May 6, 2000. Available from: https://zakon.rada.gov.ua/laws/show/770-2000-%D0%BF#Text.
Karila L, Reynaud M. GHB and synthetic cathinones: clinical effects and potential consequences. Drug Test Anal. 2011; 3(9): 552-9. DOI: 10.1002/dta.210. DOI: https://doi.org/10.1002/dta.210
Baron M, Elie M, Elie L. An analysis of legal highs: do they contain what it says on the tin? Drug Test Anal. 2011; 3(9): 576-81. doi: 10.1002/dta.274. DOI: https://doi.org/10.1002/dta.274
Bernard C, Werse B, Schell-Mack C. MoSyD. JAHRESBERICHT 2012. Drogentrends in Frankfurt am Main. Centre for Drug Research; 2013. Available from: https://www.uni-frankfurt.de/51782964/MoSyD-Jahresbericht-2012.pdf.
Petyunin GP, Polyakh AM, Shepitko VYu. Narcotic drugs, psychotropic substances and precursors. Dictionary and reference for law enforcement officers. Kharkiv: Pravo; 2006. 96 р.
Yerko DV. Expert research on α-pyrrolidinovalerophenone (α-PVP). In: Actual problems of chemistry: research and prospects. All-Ukrainian scientific conference (April 29, 2020). Zhytomyr: Publisher O. O. Evenok; 2020. Ukrainian.
Spirina ID, Fedenko ES, Shornikov AV. The problem of "designer" drugs in Ukraine. Health of Ukraine. 2018; 2(45): 48-49. Ukrainian.
Shima N, Katagi M, Kamata H. Metabolism of the newly encountered designer drug apyrrolidinovalerophenone in humans: identifications and quantitation of urinary metabolites. Forensic Toxicol. 2014; 32: 59-67. DOI: https://doi.org/10.1007/s11419-013-0202-9
Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F. Mephedrone, new kid for the chop? Addiction. 2011; 106(1): 154-61. doi: 10.1111/j.1360-0443.2010.03130.x. DOI: https://doi.org/10.1111/j.1360-0443.2010.03130.x
Psychonaut Web Mapping Research Group. Spice report. King’s College London. Institute of psychiatry. London; 2009. 14 p.
Ross EA, Watson M, Goldberger B. "Bath salts" intoxication. N Engl J Med. 2011;365(10):967-8. DOI: 10.1056/NEJMc1107097 DOI: https://doi.org/10.1056/NEJMc1107097
Dickson AJ, Vorce SP, Levine B, Past MR. Multiple-drug toxicity caused by the coadministration of 4-methylmethcathinone (mephedrone) and heroin. J Anal Toxicol. 2010; 34(3): 162-8. DOI: 10.1093/jat/34.3.162. DOI: https://doi.org/10.1093/jat/34.3.162
Europäische Beobachtungsstelle für Drogen und Drogensucht. Europäischer Drogenbericht. Trends und Entwicklungen. Luxemburg: Amt für Veröffentlichungen der Europäischen Union, 2013. Available from: http://www.emcdda.europa.eu/attachements.cfm/att_213154_DE_TDAT13001DEN1.pdf.
Meyer MR, Wilhelm J, Peters FT, Maurer HH. Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem. 2010; 397(3): 1225-33. DOI: 10.1007/s00216-010-3636-5. DOI: https://doi.org/10.1007/s00216-010-3636-5
Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH. Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology. 2014;87: 206-13. DOI: 10.1016/j.neuropharm.2014.02.016. DOI: https://doi.org/10.1016/j.neuropharm.2014.02.016
Peters FT, Meyer MR, Fritschi G, Maurer HH. Studies on the metabolism and toxicological detection of the new designer drug 4'-methyl-alpha-pyrrolidinobutyrophenone (MPBP) in rat urine using gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 824 (1-2): 81-91. DOI: 10.1016/j.jchromb.2005.07.003. DOI: https://doi.org/10.1016/j.jchromb.2005.07.003
Matsuta S, Shima N, Kamata H, Kakehashi H, Nakano S, Sasaki K, Kamata T, Nishioka H, Miki A, Katagi M, Zaitsu K, Sato T, Tsuchihashi H, Suzuki K. Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: identification and quantification of the phase I metabolites in urine. Forensic Sci Int. 2015;249: 181-8. DOI: 10.1016/j.forsciint.2015.02.004. DOI: https://doi.org/10.1016/j.forsciint.2015.02.004
Paillet-Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D. Emerging drugs of abuse: current perspectives on substituted cathinones. Subst Abuse Rehabil. 2014;5: 37-52. DOI: 10.2147/SAR.S37257. DOI: https://doi.org/10.2147/SAR.S37257
Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8(1): 33-42. DOI: 10.1007/s13181-011-0193-z. DOI: https://doi.org/10.1007/s13181-011-0193-z
Freeman TP, Morgan CJ, Vaughn-Jones J, Hussain N, Karimi K, Curran HV. Cognitive and subjective effects of mephedrone and factors influencing use of a 'new legal high'. Addiction. 2012; 107(4): 792-800. doi: 10.1111/j.1360-0443.2011.03719.x. DOI: https://doi.org/10.1111/j.1360-0443.2011.03719.x
Belton P, Sharngoe T, Maguire FM, Polhemus M. Cardiac infection and sepsis in 3 intravenous bath salts drug users. Clin Infect Dis. 2013;56(11): e102-4. DOI: 10.1093/cid/cit095 DOI: https://doi.org/10.1093/cid/cit095
Spiller HA, Ryan ML, Weston RG, Jansen J. Clinical experience with and analytical confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States. Clin Toxicol (Phila). 2011;49(6): 499-505. DOI: 10.3109/15563650.2011.590812. DOI: https://doi.org/10.3109/15563650.2011.590812
Torrance H, Cooper G. The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic Sci Int. 2010;202(1-3): e62-3. DOI: 10.1016/j.forsciint.2010.07.014. DOI: https://doi.org/10.1016/j.forsciint.2010.07.014
Slyusar VV. Basic aspects and principles of rehabilitation in a specialized narcological department. Ukrainian Bulletin of Psychoneurology. 2014;3(80): 112-4.
Terminology and Information on Drugs. Third edition. New York: United Nations; 2016. 83 р.
Goldberg J, Gardos G, Cole JO. A controlled evaluation of pyrovalerone in chronically fatigued volunteers. Int Pharmacopsychiatry. 1973;8(1): 60-9. DOI: 10.1159/000467975. DOI: https://doi.org/10.1159/000467975
Zawilska JB, Wojcieszak J. Designer cathinones--an emerging class of novel recreational drugs. Forensic Sci Int. 2013;231(1-3): 42-53. DOI: 10.1016/j.forsciint.2013.04.015. DOI: https://doi.org/10.1016/j.forsciint.2013.04.015
Maskell PD, De Paoli G, Seneviratne C, Pounder DJ. Mephedrone (4-methylmethcathinone)-related deaths. J Anal Toxicol. 2011;35(3): 188-91. DOI: 10.1093/anatox/35.3.188. DOI: https://doi.org/10.1093/anatox/35.3.188
Regan L, Mitchelson M, Macdonald C. Mephedrone toxicity in a Scottish emergency department. Emerg Med J. 2010;28(12): 1055-8. DOI: 10.1136/emj.2010.103093. DOI: https://doi.org/10.1136/emj.2010.103093
Centers for Disease Control and Prevention (CDC). Emergency department visits after use of a drug sold as "bath salts"--Michigan, November 13, 2010-March 31, 2011. MMWR Morb Mortal Wkly Rep. 2011;60(19): 624-7.
Henry JA, Fallon JK, Kicman AT, Hutt AJ, Cowan DA, Forsling M. Low-dose MDMA ("ecstasy") induces vasopressin secretion. Lancet. 1998;351(9118): 1784. DOI: 10.1016/S0140-6736(05)78744-4. DOI: https://doi.org/10.1016/S0140-6736(05)78744-4
Recommended methods for the Identification and Analysis of Synthetic Cathinones in Seized Materials. Manual for Use by National Drug Analysis Laboratories. United Nations. New York; 2015. 46 р.
Petyunin GP, Chubenko OV, Dmitrievska ZhV. Methods of detection of narcotic drugs and psychotropic substances in human biological fluids. Methods of preliminary express diagnostics (methodological recommendations). Kyiv; 2006. Ukrainian.
Recommended methods for the detection and assay of heroin, cannabinoids, cocain, amphetamine, methamphetamine and ring-substituted amphetamine derivatives in biological specimens. Manual for Use by National laboratories. New York: UN; 1995. 92 p.
Petyunin GP, Chubenko AV, Нuzenko NV. Study of some medicinal and narcotic drugs - analogues in structure and action by chromatography in thin layers of sorbent. Theory and practice of forensic examination and criminology. 2011;11: 378-84. Ukrainian.
Moffat A.C, Osselton M.D, Widdop B, Watts J, eds. Clarke's Analysis of Drugs and Poisons. Fourth Edition. London: Pharmaceutical Press; 2011.
Petyunin GP, Chubenko AV, Нuzenko NV. The use of new reagents - developers in the study of some psychotropic drugs by chromatography in thin layers of sorbent. Theory and practice of forensic examination and criminology. 2013;13: 300-5. Ukrainian.
Khizhnichenko OV, Huzenko NV, Chubenko OV. Chemical and toxicological research of new drugs - potential objects of non-medical use by chromatography in thin layers of sorbent. Pharmaceutical Journal. 2012;6: 74-7. Ukrainian.
Khizhnichenko OV, Petyunin GP. Detection of dextropropoxyphene, opiates, phenylalkylamines, tramadol and their metabolites in the joint presence in biological material. Current issues of pharmaceutical and medical science and practice. 2007; ХХ: 309.
Chorna OV, Chubenko OV, Kachalova TE. Some aspects of non-medical use of drugs in Ukraine: social aspect.. Bulletin of the National Technical University "KhPI". Series: 68. Actual problems of the development of Ukrainian society. 2022; 1: 64-71. Ukrainian. DOI: https://doi.org/10.20998/2227-6890.2022.1.11
Thin-Layer Chromatographic Rf Values of Toxicologically Relevant Substances on Standardized Sysmtes. 2nd ed. Wiley-VCH; 1992. 308 р.
Petyunin GP, Chubenko AV, Нuzenko NV. Modification of the "TLC screening" method for some controlled compounds. Theory and practice of forensic examination and criminology. 2014;14: 258-264. Ukrainian.
Guidelines for the import and export of drug and precursor reference standards for use by national drug testing laboratories and competent national authorities. New York: United Nations; 2007.
Medical laboratories. Quality and competence requirements. (ISO 15189:2012, IDT) DSTU ISO 15189:2012 (draft, first edition). Kyiv; 2015. Ukrainian.
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