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  • Chemical analysis and in vitro cytotoxicity assessment of synthetic cathinones found in seized products
    Publication . Gonçalves, João Luís Jesus; Câmara, José Sousa; Teixeira, Helena Maria de Sousa Ferreira e
    The abuse of synthetic cathinones (SCat) represents a serious public health problem, and despite the legislative efforts to control the availability and use of these substances, new derivatives continue to appear in the market. Monitoring these substances is a challenging task faced by forensic and toxicological laboratories, due to the closely related molecular structures that lead to similar analytical characteristics. Moreover, with the emergence of new substances, information about their potential toxicity is unknown and the effects can be dangerous and unpredictable. The first purpose of this work was to chemically characterize fourteen seized products suspected to contained SCat, using several complementary analytical techniques, namely infrared spectroscopy (IR), gas chromatography coupled to mass spectrometry (GC-MS), ultrahigh performance liquid chromatography with photodiode array detector (UHPLC-PDA) and nuclear magnetic resonance (NMR). It was possible to identify nine SCat, namely methylone, methedrone, N-ethylcathinone, buphedrone, pentedrone, 3-fluoromethcathinone (3-FMC), 4- fluoromethcatinone (4-FMC), α-pyrrolidinohexanophenone (α-PHP) and 4-methyl-α pyrrolidinohexanophenone (MPHP). Subsequently, a new analytical methodology, based on the microextraction technique μSPEed® followed by UHPLC-PDA analysis, was developed for the determination of SCat in urine samples. Under the optimized conditions, the method showed satisfactory results in terms of linearity, with determination coefficients (R2 ) > 0.998, within the studied concentration ranges, and low detection limits (LOD) ranging from 36.8 to 95.3 ng mL−1. Once validated, the method was applied to real samples and α-PHP was detected in several samples. The cytotoxic potential of SCat, individually and in the samples, was evaluated in HepG2 cells. The elucidation of the cellular mechanisms underlying the observed hepatotoxicity, particularly those involved in oxidative stress was also evaluated. MPHP and α-PHP were the most cytotoxic compounds, and all SCat were able to disrupt the balance between reactive oxygen and nitrogen species (ROS and RNS) generation and the scavenging capacity of the antioxidant system.
    2023-04-19Doctoral thesis Embargoed access Show more