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Percorrer por autor "Langa, Ivan"

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  • Enantiomeric biodistribution and toxicity of 3-chloromethcathinone (3-CMC) in Wistar rats after acute exposure – preliminary data
    Publication . Langa, Ivan; Rocha-Pereira, Carolina; Milhazes, Nuno; Silva, Diana Dias da; Domingues, Susana; Silva, Paula; Barbosa, Joana; Faria, Juliana; Tiritan, Maria Elizabeth; Ribeiro, Cláudia; Dias da Silva, Diana Cristina
    There has been a surge in global attention to New Psychoactive Substances (NPS) [1]. Synthetic cathinones stand out as a widely consumed NPS class. Notably, 3-chloromethcathinone (3-CMC) accounted for over 34% of NPS seizures in 2021 [2], which underscores concerns regarding its consumption and health effects. Of note, 3-CMC is chiral and mostly sold as a racemate. As human me-tabolism and pharmacological effects can be enantioselective [3], determination of the impact of enanti-oselectivity in toxicokinetics/toxicodynamics is essential for the assessment of 3-CMC effects. This work aimed to evaluate in vivothe enantioselective biodistribution and toxicity of racemic 3-CMC, after an acute exposure to 3-CMC. Ten-week-old male Wistar rats were administered intraperitoneally with saline or 3-CMC (10 or 20 mg/kg; n=6). Twenty-four hours after, animals were deeply anesthetized and nine organs (brain, liver, kidneys, lungs, heart, spleen, gut, muscle, adipose tis-sue), blood and urine were collected. For evaluation of the enantiomeric biodistribution, a previous in houseestablished indirect method by gas chromatography [3], was adapted and validated. Some biochem-ical analysis was performed using an analyser, whereas TBARS, ATP, glutathione and total protein were determined by spectrophotometry. Organs were also processed for histological analysis. After 24 h, 3-CMC was not found in most organs. Both enantiomers were detected in urine with one dominant enantiomer, suggesting enantioselectivity in metabolism. The histopathological results showed possible central chromatolysis in the brain (20 mg/kg), liver inflammation, renal lesions, lungs’ haemoptysis, and alveolar haemorrhage, in most 3-CMC-exposed animals. No differences were observed inthe heart. Our findings show rapid 3-CMC renal elimination, with enantio selectivity in metabolism. Alt-hough biochemical evaluations are ongoing, the results are expected to give further insights on the 3-CMC toxicity and histological abnormalities found in the brain, kidneys, liver and lungs.
    2024-05-01Comunicação em conferência Acesso aberto Ver mais
  • Enantioseparationof 3-chloromethcathinone by liquid chromatography at the milligram scale
    Publication . Langa, Ivan; Ribeiro, Cláudia; Gonçalves, Virgínia; Dias da Silva, Diana; Cravo, Sara; Tiritan, Maria; Dias da Silva, Diana Cristina
    The most prominent synthetic cathinone (SCAT)is 3-chloromethcathinone (3-CMC), accounting for 34% and 63.41% of the total seized new psychoactive substances (NPS) in Europe in 2021 and 2022, respectively [1, 2].Over the latest years, since the first identification on the European drug market in September 2014 in Sweden, 3-CMC has gained significant popularity among the younger drug users [3]. Moreover, 3-CMC is chiral and its enantiomers can show different biological activity, highlighting the importance of the enantio selectivity studies in clinical, forensic and ecotoxicological context. The aim of this study was to optimize a chromatographic method for the enantiomeric separation of 3-CMC at the milligram scale for further use in in vitroand ecotoxicity assessments. The enantio separation as well as the enantiomeric purity evaluation of the 3-CMC were performed by liquid chromatography coupled to the ultraviolet-visible detector (UV/Vis), using a CHIRALPAK®AD-H 10x250mm, 5 μm, a semi-preparative column. A Dionex Ultimate 3000 automated fraction collector was used for fractions collection. Data was analyzed by Chromeleon 7.0 software. For method conditions optimization, a solution at 100 μgmL-1of 3-CMC in ethanol with diethylamine was used. The optimized method allowed the separation of the enantiomers of 3-CMCat final concentration of 3.7 mg mL-1, with an enantiomeric purity of 98 % and 95 % for the first and second eluted enantiomer, respectively. The determination of the absolute configuration of theenantiomers is ongoing by electronic circular dichroism. The isolated enantiomers will be used for the enantio selective evaluation of the 3-CMC ecotoxicity.The determination of the absolute configuration of the enantiomers will enable correlating the ecotoxicity of each enantiomer.
    2025-05-27Póster em conferência Acesso aberto Ver mais