TOXICOLOGY OF NEW PSYCHOACTIVE SUBSTANCES: ANALYTICAL TECHNIQUES AND LEGAL IMPLICATIONS IN FORENSIC INVESTIGATIONS
Main Article Content
Keywords
Metabolic profiling, forensic toxicology, drug regulation, biochemical markers, analytical validation.
Abstract
The emergence of novel psychoactive drugs has greatly complicated the identification and interpretation of these drugs in the clinical toxicology and forensic medicine arenas. In essence, these are chemically modified forms of controlled drugs that are already under control and are to avoid legislation and as such, cause unpredictable pharmacological and toxicological effects. It is crucial to determine and accurately identify the New Psychoactive Substances and interpret them through creative diagnostic and medico-legally reliable techniques. Multi-matrix detection and structure elucidation with the help of liquid chromatography-tandem mass spectrometry, gas chromatography-mass spectrometry, Fourier-transform infrared spectroscopy and nuclear magnetic resonance were applied in the present study, along with an integrative toxicological approach. The following validation parameters have been covered among others; linearity, sensitivity, precision, and recovery, and biochemical tests of liver and muscle enzymes, as biomarkers of toxicity. The findings showed that LC-MS/MS had greater analytical sensitivity, recovery, and repeatability compared to GC-MS, thus it was to be used in complicated biological samples. The level of NPS was high in urine samples which indicates the usefulness of this route not only in excretion but also in detection. The presence of high aminotransferases, creatine kinase and lactate dehydrogenase showed liver and muscle damage in case of consumption of NPS. Implementation of the suggested analytical-biochemical system has broadened the prospects of identification, clinical behavior, and prosecution of NPS data. In that regard, the authors propose methodological standardization, inter-laboratory harmonization, and international toxicovigilance as the measures needed to enhance the monitoring capacity of NPS in order to provide global safety of population health and reinforce the scientific credibility of forensic toxicology.
References
2. Ferrari Júnior E, Leite BH, Gomes EB, Vieira TM, Sepulveda P, Caldas ED. Fatal cases involving new psychoactive substances and trends in analytical techniques. Frontiers in Toxicology. 2022 Oct 25;4:1033733.
3. Giorgetti A, Pascali JP, Fais P, Pelletti G, Gabbin A, Franchetti G, Cecchetto G, Viel G. Molecular mechanisms of action of novel psychoactive substances (NPS). A new threat for young drug users with forensic-toxicological implications. Life. 2021 May 14;11(5):440.
4. Flanagan RJ, Cuypers E, Maurer HH, Whelpton R. Fundamentals of analytical toxicology: Clinical and forensic. John Wiley & Sons; 2020 Aug 3.
5. Shapovalov V. Interdisciplinary legal, forensic and pharmaceutical, forensic and chemical, forensic and narcological, forensic and toxicological, criminal and legal study of the illegal trafficking of Amphetamine. SSP Modern Law and Practice. 2023 Aug 8;3(3):1-4.
6. Grafinger KE, Liechti ME, Liakoni E. Clinical value of analytical testing in patients presenting with new psychoactive substances intoxication. British journal of clinical pharmacology. 2020 Mar;86(3):429-36.
7. Vicente JL, Chassaigne H, Holland MV, Reniero F, Kolář K, Tirendi S, Vandecasteele I, Vinckier I, Guillou C. Systematic analytical characterisation of new psychoactive substances: a case study. Forensic Science International. 2016 Aug 1;265:107-15.
8. de Campos EG, De Martinis EC, De BS. Forensic Analysis of Illicit Drugs and Novel Psychoactive Substances in Wastewater. Brazilian Journal of Analytical Chemistry. 2022;9(34):15-34.
9. Elliott S, Sedefov R, Evans‐Brown M. Assessing the toxicological significance of new psychoactive substances in fatalities. Drug testing and analysis. 2018 Jan;10(1):120-6.
10. Dinis-Oliveira RJ, Magalhães T. Abuse of licit and illicit psychoactive substances in the workplace: medical, toxicological, and forensic aspects. Journal of Clinical Medicine. 2020 Mar 12;9(3):770.
11. Bruni AT, Rodrigues CH, dos Santos C, de Castro JS, Mariotto LS, Sinhorini LF. Analytical challenges for identification of new psychoactive substances: a literature-based study for seized drugs. Brazilian Journal of Analytical Chemistry. 2021 Sep 29;9(34):52-78.
12. Dargan PI, Wood DM, editors. Novel psychoactive substances: classification, pharmacology and toxicology. Academic Press; 2021 Sep 6.
13. Hasegawa K, Suzuki O. Toxicological analysis on forensic investigation in drug-related cases; pharmacological information on 88 psychoactive substances in “Narcotics and Psychotropics Control Act” in Japan. Medical mass spectrometry. 2022 Jun 25;6(1):2-6.
14. Santos IC, Maia D, Dinis-Oliveira RJ, Barbosa DJ. New psychoactive substances: health and legal challenges. Psychoactives. 2024 Jun 1;3(2):285-302.
15. Labay LM, Bitting CP, Legg KM, Logan BK. The Determination of Insulin Overdose in Postmortem Investigations. Acad Forensic Pathol. 2016 Jun;6(2):174-183. doi: 10.23907/2016.019. Epub 2016 Jun 1. PMID: 31239889; PMCID: PMC6507008.
16. Mellouki Y, Sellami L, Saker L, Belkhadja N, Zerairia Y, Kaious F, Mira AH. The epidemiological and medico-legal characteristics of violent deaths and spousal homicides through a population of women autopsied within the Forensic Medicine Department of the University Hospital of Annaba. BMC Women's Health. 2023 Mar 25;23(1):129. doi: 10.1186/s12905-023-02287-2. PMID: 36964556; PMCID: PMC10039587.
17. Cardinale AN, Di Lorenzo A, Bellino M, Strisciullo G, Mussi V, Sablone S. Thanatochemistry and the role of hypoxanthine in the post-mortem interval estimation: a systematic literature review. Int J Legal Med. 2025 Jul;139(4):1743-1780. doi: 10.1007/s00414-024-03378-x. Epub 2025 Feb 22. PMID: 39985608; PMCID: PMC12170682.
18. Tarda L, Sacco MA, Tarzia P, Verrina MC, Calafiore J, Aquila I. Analysis of toxicological findings related to immunofluorescence investigations. Clin Ter. 2024 Jul-Aug;175(Suppl 2(4)):183-186. doi: 10.7417/CT.2024.5112. PMID: 39101422.
19. Rubio NC, Herbello-Hermelo P, Álvarez-Freire I, Cabarcos-Fernández P, Tabernero-Duque MJ, Sánchez-Sellero I, Bermejo-Barrera P, Bermejo-Barrera AM, Moreda-Piñeiro A. Impact of coca leaf flour candy consumption on cocaine and benzoylecgonine levels: The role of hygrine and cuscohygrine in distinguishing licit from illicit cocaine use. Forensic Sci Int. 2025 Jun;371:112494. doi: 10.1016/j.forsciint.2025.112494. Epub 2025 May 6. PMID: 40359777.
20. Aheri A, Daerqaoui MA, Belamine F, Belhouss A, Benyaich H. Handling Complaints Related to Diagnostic Faults Before Disciplinary Bodies: Analysis of French Ordinal Jurisprudence. Cureus. 2025 Feb 24;17(2):e79564. doi: 10.7759/cureus 79564. PMID: 40144406; PMCID: PMC11939835.
21. Gerona R. Designer Drugs: Chemistry, Analysis, Regulation, Toxicology, Epidemiology & Legislation of New Psychoactive Substances. Elsevier; 2024 Jan 17.
22. Casparsen C. The role of toxicology in forensic investigations. International Journal of Forensic Medicine. 2024;6(1):31-33. doi:10.33545/27074447.2024.v6.i1a.76
23. Saba A. Forensic Toxicology: Advances in the Identification of New Psychoactive Substances (NPS). Int J Forens Sci. 2025;10(1):000430. doi:10.23880/ijfsc-16000432.
24. Singh Z. Forensic toxicology: biological sampling and use of different analytical techniques. Forensic Research & Criminology International Journal. 2017;4(4):117-20.
25. Kintz P. Hair analysis in forensic toxicology: an updated review with a special focus on pitfalls. Current Pharmaceutical Design. 2017 Oct 1;23(36):5480-6.
