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Review
. 2022 Oct 25:4:1033733.
doi: 10.3389/ftox.2022.1033733. eCollection 2022.

Fatal cases involving new psychoactive substances and trends in analytical techniques

Ettore Ferrari Júnior  1   2 , Bruno Henrique Monteiro Leite  1 , Eliude Barbosa Gomes  1 , Tales Mateus Vieira  3 , Pedro Sepulveda  4 , Eloisa Dutra Caldas  2
Affiliations
Review

Fatal cases involving new psychoactive substances and trends in analytical techniques

Ettore Ferrari Júnior et al. Front Toxicol. .

Abstract

New psychoactive substances (NPS) are an emerging public health issue and deaths are commonly associated with polydrug abuse. Moreover, the number of new substances available is constantly increasing, causing intoxications in low doses, characteristics that impose to toxicology and forensic laboratories to keep routine methods up to date, with high detectability and constantly acquiring new analytical standards. Likewise, NPS metabolites and respective elimination pathways are usually unknown, making it difficult the detection and confirmation of the drug involved in the fatal case in an analytical routine. A literature search was performed on PubMed, Scopus and Web of Science databases for papers related to chromatographic analyses from fatal cases related to NPS use published from 2016 to 2021. A total of 96 papers were retrieved and reviewed in this study. Opioids, synthetic cathinones, phenethylamines/amphetamines and cannabinoids were the NPS classes most found in the fatal cases. In many cases, multiple compounds were detected in the biological samples, including prescription and other illegal drugs. Liquid chromatography-tandem mass spectrometry, an alternative to overcome the gas chromatography-mass spectrometry limitations for some compounds, was the analytical technique most used in the studies, and high resolution mass spectrometry was often applied to NPS metabolite investigation and structural characterization and identification of unknown compounds. Toxicological screening and quantitation methods need to be continuously updated to include new substances that are emerging on the drug market that can be fatal at very low doses.

Keywords: GC-MS; HRMS; LC-MS/MS; fatal cases; new psychoactive substances; opioids; synthetic cathinones.

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Conflict of interest statement

TV was employed by Brainfarma Pharmaceutical Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chemical structure of the main compounds from the NPS classes discussed in this paper. 25I-NBOMe (A) and amphetamine (B), highlighting the phenethylamine core (red); the synthetic cathinone N-ethylpentylone (C), highlighting the cathinone core (red); m-CPP (D), highlighting the piperazine core (red); 5-MeO-MIPT (E), highlighting the tryptamine core (red); Opioids: fentanyl analog crotonylfentanyl (F) and U-47700 (G); phencyclidine (H) and the analogue ketamine (I); designer benzodiazepine diclazepam (J); synthetic cannabinoid JWH-210 (K); 2-Aminoindane (L).
FIGURE 2
FIGURE 2
Paper selection strategy.
FIGURE 3
FIGURE 3
Main NPS classes reported in the publications from 2016 to 2021. Others: piperazine (2016), tryptamine (2017–2021), indole alkaloids found in kratom (2018 and 2019); methaqualone analog (2020). Amphetamine analogs were included in phenethylamine data. Opioid includes fentanyl and analogs.
See this image and copyright information in PMC

References

    1. Adamowicz P., Bakhmut Z., Mikolajczyk A. (2020b). Screening procedure for 38 fentanyl analogues and five other new opioids in whole blood by liquid chromatography-tandem mass spectrometry. J. Appl. Toxicol. 40, 1033–1046. 10.1002/jat.3962 - DOI - PubMed
    1. Adamowicz P., Gieroń J., Gil D., Lechowicz W., Skulska A., Tokarczyk B., et al. (2016). Blood concentrations of α-pyrrolidinovalerophenone (α-PVP) determined in 66 forensic samples. Forensic Toxicol. 34, 227–234. 10.1007/s11419-016-0306-0 - DOI
    1. Adamowicz P., Jurczyk A., Gil D., Szustowski S. (2020a). A case of intoxication with a new cathinone derivative α-PiHP – a presentation of concentrations in biological specimens. Leg. Med. 42, 101626. 10.1016/j.legalmed.2019.101626 - DOI - PubMed
    1. Adamowicz P., Meissner E., Maślanka M. (2019). Fatal intoxication with new synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA. Clin. Toxicol. 57, 1103–1108. 10.1080/15563650.2019.1580371 - DOI - PubMed
    1. Al-Matrouk A., Alqallaf M., Alshemmeri A., Bojbarah H. (2019). Identification of synthetic cannabinoids that were seized, consumed, or associated with deaths in Kuwait in 2018 using GC – MS and LC – MS-MS analysis. Forensic Sci. Int. 303, 109960. 10.1016/j.forsciint.2019.109960 - DOI - PubMed