Determinação de benzodiazepínicos em plasma por cromatografia líquida com detector ultravioleta-visível empregando microextração líquido-líquido dispersiva

• Autor(a) principal: Saldanha, Geovane de Almeida
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Manancial - Repositório Digital da UFSM
• Texto Completo: http://repositorio.ufsm.br/handle/1/21163
• topic: Microextração líquido-líquido dispersiva; Benzodiazepínicos; Plasma; Cromatografia líquida; Intoxicações; Dispersive liquid-liquid microextraction; Liquid chromatography; Intoxications; CNPQ::CIENCIAS DA SAUDE::FARMACIA

Drugs has been the main agents involved in intoxications in Brazil. According to the latest report of SINITOX, these agents summed up 20367 cases representing 26,79% of all agents involved. Among them, 9983 cases were suicide attempts. Psychotropic drugs of the benzodiazepine class were the agents with bigger representativity in this scenario. Among them, Clonazepam (Rivotril®) was involved in 1506 cases (1223 under intentional circumstance). Benzodiazepines possess pharmacological characteristics convenient for suicide attempts and as drug facilitated crimes. As these characteristics are not exclusive of this drug class, it is necessary a development of an analytical method capable of detect and quantify these drugs with adequate specificity and sensitivity to help in the doctor behavior and other health professionals in accidental or intentional intoxications. In this context, blood is considered a complex matrix that allows to determine the concentration of this xenobiotic which is still active in the organism, allowing to correlate its levels with the biological effects, besides being a sample of choice for toxicological analysis. However, extractive procedures are necessary as previous step to promote biological matrix clean up, avoiding equipment damage and to other inputs as concentrate the analytes of interest allowing the chromatographic system detection. Among the extractive techniques, the dispersive liquid-liquid microextraction (DLLME) stands out for being a quick, simple, low cost process adaptable in any laboratory and it was little explored for the purpose of toxicological analyses. The main objective of this research was the development for an analytical method for the benzodiazepine analysis in plasma aiming to improve the medical behavior in accidental or intentional intoxications from the Hospital Universitário de Santa Maria located in the Universidade Federal de Santa Maria (HUSMUFSM). The results revealed that the extractive procedure got optimized this way, from 500 μL of plasma, previously alkalized to pH 10, are added 0,013 g of sodium chloride, then 400 μL of chloroform and 700 μL of acetonitrile are injected simultaneously, the content is homogenized in vortex for 10 seconds, then it is placed under ultrasonic bath por 1 minute, then the tube is centrifuged by 10000 rpm/10 minutes, the organic phase is collected, dried and resurrected with 30 μL of mobile phase (water pH 9/methanol/acetonitrile, 63:19:18) and 20 μL in the HPLCDAD. In the analytical validation, according to UNODC and SWGTOX guides, it wasn’t possible to validate all the parameters, it is possible to apply this method only for screening.