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Desenvolvimento de uma metodologia analítica para a análise de dextrometorfano e seus metabolitos maioritários em amostras biológicas
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Abstract(s)
O dextrometorfano (DXM), quimicamente referido como 3-metoxi-17-meilmorfinano é a substância ativa de alguns medicamentos não sujeitos a receita médica, indicados no tratamento sintomático da tosse seca. O DXM e o seu principal metabolito, dextrorfano (DXO) apresentam sintomas semelhantes ao de drogas dissociativas quando consumidos para além das doses recomendadas. A dose máxima diária recomendada de DXM é de 120 mg.
Os possíveis problemas relacionados com o abuso de medicamentos que contenham uma substância ativa a possibilidade de apresentar capacidades dissociativas justificam o desenvolvimento de novos métodos analíticos.
Numa fase inicial realizou-se uma pesquisa sobre as propriedades físico-químicas dos compostos. Posteriormente, tentou-se desenvolver um método de extração, utilizando a microextração em fase sólida (SPME), para detetar os analitos em sangue. Foram testadas duas fibras SPME-LC Tips, fibras C18 e PDMS/DVB. Construiu-se um desenho experimental, um Plackett Burman, para otimizar o processo de extração. Identificou-se o pH como uma das variáveis com maior influência.
A análise quantitativa e qualificativa realizou-se através cromatografia gasosa com recurso a dois analisadores de massa diferentes: um analisador de voo (GC-TOF/MS) e um espectrómetro de massa em tandem (GC/MS/MS), utilizando um triplo quadrupolo.
No decorrer do trabalho, foi necessário a substituição do padrão interno, inicialmente escolhido, assim como o uso de protetores analíticos, numa tentativa de aumentar os picos cromatográficos dos compostos.
Após realizadas diversas injeções e analisados os resultados ao longo do processo experimental, verificou-se que o uso de sangue total apresentava desvantagens como a sujidade no liner e das fibras tips.
Dextromethorphan (DXM), chemically referred to as 3-methoxy-17-meylmorphinan, is the active substance in some over-the-counter medicines indicated in the symptomatic treatment of dry cough. DXM and its main metabolite, dextrorphan (DXO) exhibit symptoms similar to dissociative drugs when consumed in excess of recommended doses. The maximum recommended daily dose of DXM is 120 mg. The possible problems related to the abuse of drugs that contain an active substance, the possibility of presenting dissociative abilities, justify the development of new analytical methods. In an initial phase, research was carried out on the physicochemical properties of the compounds. Subsequently, an attempt was made to develop an extraction method, using solid phase microextraction (SPME), to detect the analytes in blood. Two SPME-LC Tips fibers, C18 and PDMS/DVB fibers were tested. An experimental design, a Plackett Burman, was built to optimize the extraction process. PH was identified as one of the most influential variables. The quantitative and qualitative analysis were performed resorting gas chromatography using two different mass analyzers: a flight analyzer (GC-TOF/MS) and a tandem mass spectrometer (GC/MS/MS), using a triple quadrupole. During the work, it was necessary to replace the internal standard, initially chosen, as well as the use of analytical protectors, in an attempt to increase the chromatographic peaks of the compounds. After performing several injections and analyzing the results throughout the experimental process, it was found that the use of whole blood had disadvantages such as dirt on the liner and tips fibers.
Dextromethorphan (DXM), chemically referred to as 3-methoxy-17-meylmorphinan, is the active substance in some over-the-counter medicines indicated in the symptomatic treatment of dry cough. DXM and its main metabolite, dextrorphan (DXO) exhibit symptoms similar to dissociative drugs when consumed in excess of recommended doses. The maximum recommended daily dose of DXM is 120 mg. The possible problems related to the abuse of drugs that contain an active substance, the possibility of presenting dissociative abilities, justify the development of new analytical methods. In an initial phase, research was carried out on the physicochemical properties of the compounds. Subsequently, an attempt was made to develop an extraction method, using solid phase microextraction (SPME), to detect the analytes in blood. Two SPME-LC Tips fibers, C18 and PDMS/DVB fibers were tested. An experimental design, a Plackett Burman, was built to optimize the extraction process. PH was identified as one of the most influential variables. The quantitative and qualitative analysis were performed resorting gas chromatography using two different mass analyzers: a flight analyzer (GC-TOF/MS) and a tandem mass spectrometer (GC/MS/MS), using a triple quadrupole. During the work, it was necessary to replace the internal standard, initially chosen, as well as the use of analytical protectors, in an attempt to increase the chromatographic peaks of the compounds. After performing several injections and analyzing the results throughout the experimental process, it was found that the use of whole blood had disadvantages such as dirt on the liner and tips fibers.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
Keywords
Dextrometorfano Dextrorfano Preparação de amostra Método de análise SPME LC-Tips Sangue total