Synthesis of emerging cathinones and validation of a SPE GC-MS method for their simultaneous quantification in blood.

Autor: Júlio S; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal.; Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Rua Larga, 3004-535, Coimbra, Portugal., Ferro RA; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal., Santos S; Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal., Alexandre A; Laboratório de Polícia Científica da Polícia Judiciária - Setor de Drogas e Toxicologia, Rua Gomes Freire, 1169-007, Lisbon, Portugal., Caldeira MJ; Laboratório de Polícia Científica da Polícia Judiciária - Setor de Drogas e Toxicologia, Rua Gomes Freire, 1169-007, Lisbon, Portugal., Franco J; Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Sul, Serviço de Química e Toxicologia Forenses, Rua Manuel Bento de Sousa, 3, 1169-201, Lisbon, Portugal., Barroso M; Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. - Delegação do Sul, Serviço de Química e Toxicologia Forenses, Rua Manuel Bento de Sousa, 3, 1169-201, Lisbon, Portugal. mario.j.barroso@inmlcf.mj.pt., Gaspar H; BioISI - Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal. hmgaspar@fc.ul.pt.; MARE - Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630, Peniche, Portugal. hmgaspar@fc.ul.pt.
Jazyk: angličtina
Zdroj: Analytical and bioanalytical chemistry [Anal Bioanal Chem] 2023 Feb; Vol. 415 (4), pp. 571-589. Date of Electronic Publication: 2022 Dec 09.
DOI: 10.1007/s00216-022-04440-6
Abstrakt: Over the past 15 years, synthetic cathinones have emerged as an important class of new psychoactive substances (NPS) worldwide. The proliferation of these psychostimulants and their sought-after effects among recreational drug users pose a serious threat to public health and enormous challenges to forensic laboratories. For forensic institutions, it is essential to be one step ahead of covert laboratories, foreseeing the structural changes possible to introduce in the core skeleton of cathinones while maintaining their stimulating activity. In this manner, it is feasible to equip themselves with standards of possible new cathinones and validated analytical methods for their qualitative and quantitative detection. Therefore, the aim of the work herein described was to synthesize emerging cathinones based on the evolving patterns in the illicit drug market, and to develop an analytical method for their accurate determination in forensic situations. Five so far unreported cathinones [4'-methyl-N-dimethylbuphedrone (4-MDMB), 4'-methyl-N-ethylbuphedrone (4-MNEB), 4'-methyl-N-dimethylpentedrone (4-MDMP), 4'-methyl-N-dimethylhexedrone (4-MDMH), and 4'-methyl-N-diethylbuphedrone (4-MDEB)] and a sixth one, 4'-methyl-N-ethylpentedrone, already reported to EMCDDA and also known as 4-MEAP, were synthesized and fully characterized by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). An analytical method for the simultaneous quantification of these cathinones in blood, using solid phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS) was developed and validated. The results prove that this methodology is selective, linear, precise, and accurate. For all target cathinones, the extraction efficiency was higher than 73%, linearity was observed in the range of 10 (lower limit of quantification, LLOQ) to 800 ng/mL, with coefficients of determination higher than 0.99, and the limits of detection (LODs) were 5 ng/mL for all target cathinones. The stability of these cathinones in blood matrices is dependent on the storage conditions; 4-MNEB is the most stable compound and 4-MDMH is the least stable compound. The low limits obtained allow the detection of the compounds in situations where they are involved, even if present at low concentrations.
(© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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