CONSIDERAÇÕES FINAIS

Considerando os dados obtidos, pode-se concluir que os métodos analíticos propostos oferecem a oportunidade para obter parâmetros farmacocinéticos com uma adequada precisão e exatidão, pois estão dentro dos limites necessários exigidos pela legislação para os estudos bioequivalência e farmacocinéticos. Além disso, os ensaios são rápidos e o tempo da corrida analítica não ultrapassou os 7 minutos para os três estudos.

A capacidade de manterem-se inalterados em pequenas variações nos parâmetros caracterizou a robustez dos métodos, possibilitando a intercambialidade entre laboratórios e doseamento em outros fluidos biológicos. Possuem vantagens em termos de custos, em comparação com outros métodos descritos, pois utilizam procedimentos de preparo de amostras relativamente simples sendo desnecessária a utilização de pré-tratamento em cartuchos e pré-colunas. Nas condições cromatográficas descritas, as substâncias analíticas foram bem separadas dos padrões interno com alta sensibilidade e reprodutibilidade.

As limitações da pesquisa são possíveis influências que podem ou não ser controladas pelo pesquisador. Este tipo de abordagem está relacionado ao emprego de recursos e técnicas estatísticas que visem quantificar os dados coletados. No desenvolvimento da pesquisa de natureza quantitativa devem-se formular hipóteses e classificar a relação entre as variáveis para garantir a precisão dos resultados, evitando contradições no processo de análise e interpretação. Assim, foi observada relativa dificuldade quanto à geração, interpretação e análise dos resultados estatísticos uma vez que esses parâmetros farmacocinéticos foram processados por empresa (Pharmacience Laboratórios Ltda) especializada e autorizada pela Agência Nacional de Vigilância Sanitária.

Os métodos analíticos mostraram-se precisos, pois os coeficientes de variação para os controles de qualidade, baixo, médio e alto permaneceram abaixo de 15% e abaixo de 20% para o controle de qualidade com a mesma concentração

do limite de quantificação. Verificou-se acurácia, pois os valores médios permaneceram dentro dos 15% do valor nominal para o controle de qualidade baixo, médio e alto e não se desviou mais que 20% de limite de quantificação.

Os métodos foram considerados sensíveis, pois os menores limites de quantificação dos métodos (LQ=0,5 µg/mL; 30ng/mL; 20/40 ng/mL, para amoxicilina, norfloxacino e OXC/MHD, respectivamente) apresentaram um coeficiente de variação inferior a 20%.

Os métodos mostraram-se específicos já que não houve interferência nos tempos de retenção dos picos dos analitos superior a 20% da resposta do limite de quantificação.

A estabilidade dos métodos foi assegurada, através dos testes de congelamento e descongelamento, onde se verificou não haver degradação devido à temperatura, em 3 ciclos de congelamento e descongelamento, bem como no pós- processamento, curta e longa duração de estocagem.

Os métodos analíticos utilizados HPLC/RP e LC-MS-MS para quantificação de norfloxacino e OXC/MHD em plasma humano, desenvolvido e validado, apresentam vantagens sobre os já descritos. A quantificação de amoxicilina demonstrou resultados semelhantes aos já publicados, embora utilizando outras técnicas de detecção como espectrometria de massa.

CONCLUSÃO

Os três métodos bioanalíticos propostos foram desenvolvidos, devidamente validados e quantificam com exatidão (acurácia) e precisão (reprodutibilidade) os parâmetros farmacocinéticos de formas farmacêuticas orais de amoxicilina, norfloxacino e oxcarbazepina em plasma de voluntários sadios, de modo que são válidos para o emprego em estudos de bioequivalência que envolvam esses fármacos.

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No documento e validação de métodos bioanalíticos para quantificação da amoxicilina, norfloxacino e oxcarbazepina em estudos farmacocinéticos (páginas 159-177)