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Validação de Métodos Analíticos e Estudo de Degradação Forçada de um Anestésico Oral
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Este trabalho foi realizado na empresa Sidefarma S.A. com o objetivo
principal de validar dois métodos analíticos por cromatografia líquida de alta
eficiência: um visa quantificar o princípio ativo e os conservantes, propilparabeno e
metilparabeno, presentes no produto farmacêutico, e o outro é destinado à
quantificação de substâncias aparentadas no produto. A validação destes métodos
é fundamental para garantir a sua adequação às análises de rotina no Laboratório
de Controlo de Qualidade.
No método de doseamento, a especificidade mostrou que nenhum
composto interferiu na quantificação do princípio ativo e conservantes. As
recuperações ficaram entre os 98 e 102%. A linearidade foi excelente, com
coeficientes de correlação (r) de 1,000 para o API, 0,996 para o metilparabeno e
0,995 para o propilparabeno, apresentando resíduos na origem de 2% para o API
e metilparabeno, e 1% para o propilparabeno.
No método de substâncias aparentadas, o princípio ativo e a Impureza A
foram analisados, também sem interferências na especificidade. As recuperações
variaram entre 94 e 101%. A linearidade foi igualmente boa, com r de 0,999 tanto
para o API quanto para a Impureza A, e resíduos na origem de 0,4% e 2%,
respetivamente.
Foi realizado um estudo de degradação forçada em soluções de princípio
ativo, de placebo e de amostra, sob diferentes condições (hidrólise, oxidação,
exposição ao calor, luz UV, entre outras), confirmando a correlação entre a perda
de concentração de princípio ativo e o aumento de impurezas. A degradação por
oxidação com peróxido de hidrogénio foi a mais significativa, embora difícil de
avaliar devido a diferenças nas técnicas de preparação das amostras. O balanço
de massa variou entre 103 e 134%, e verificou-se a formação de uma impureza
desconhecida.
Por fim, foi validado um método de identificação do API por espetroscopia
FTIR-ATR, após preparação da amostra de produto acabado, da amostra de
placebo e da solução de API. Este método revelou-se específico para a
identificação do princípio ativo no produto, uma vez que se alcançou um valor de
correlação de 0,9851.
This work was performed at Sidefarma S.A. with the main goal of validating two analytical methods using high performance liquid chromatography: one aims to quantify the active pharmaceutical ingredient and the preservatives, propylparaben and methylparaben, present in the pharmaceutical product, and the other is designed to quantify related substances in the product. The validation of these methods is essential to ensure their suitability for routine analyses in the Quality Control Laboratory. In the assay method, specificity showed that no compound interfered with the quantification of API and preservatives. Recoveries obtained were between 98 and 102%. Linearity was excellent, with correlation coefficients (r) of 1,000 for API, 0,996 for methylparaben and 0,995 for propylparaben, with residues at source of 2% for API and methylparaben, and 1% for propylparaben. In the method of related substances, API and Impurity A were analysed, also without interference in specificity. Recoveries ranged from 94 to 101%. Linearity was also good, with an r of 0,999 for both API and Impurity A, and residues at source of 0,4% and 2%, respectively. A forced degradation study was carried out on active ingredient, placebo and sample solutions under different conditions (hydrolysis, oxidation, exposure to heat, UV light, among others), confirming the correlation between the loss of active ingredient concentration and the increase in impurities. Degradation by oxidation with hydrogen peroxide was the most significant, although difficult to assess due to differences in sample preparation techniques. The mass balance varied between 103 and 134%, and the formation of an unknown impurity was noted. Finally, a method for identifying API by FTIR-ATR spectroscopy was validated after preparing the finished product sample, the placebo sample and an API solution. This method demonstrated to be specific for identifying the active ingredient in the product, since a correlation value of 0,9851 was achieved.
This work was performed at Sidefarma S.A. with the main goal of validating two analytical methods using high performance liquid chromatography: one aims to quantify the active pharmaceutical ingredient and the preservatives, propylparaben and methylparaben, present in the pharmaceutical product, and the other is designed to quantify related substances in the product. The validation of these methods is essential to ensure their suitability for routine analyses in the Quality Control Laboratory. In the assay method, specificity showed that no compound interfered with the quantification of API and preservatives. Recoveries obtained were between 98 and 102%. Linearity was excellent, with correlation coefficients (r) of 1,000 for API, 0,996 for methylparaben and 0,995 for propylparaben, with residues at source of 2% for API and methylparaben, and 1% for propylparaben. In the method of related substances, API and Impurity A were analysed, also without interference in specificity. Recoveries ranged from 94 to 101%. Linearity was also good, with an r of 0,999 for both API and Impurity A, and residues at source of 0,4% and 2%, respectively. A forced degradation study was carried out on active ingredient, placebo and sample solutions under different conditions (hydrolysis, oxidation, exposure to heat, UV light, among others), confirming the correlation between the loss of active ingredient concentration and the increase in impurities. Degradation by oxidation with hydrogen peroxide was the most significant, although difficult to assess due to differences in sample preparation techniques. The mass balance varied between 103 and 134%, and the formation of an unknown impurity was noted. Finally, a method for identifying API by FTIR-ATR spectroscopy was validated after preparing the finished product sample, the placebo sample and an API solution. This method demonstrated to be specific for identifying the active ingredient in the product, since a correlation value of 0,9851 was achieved.
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Palavras-chave
Validação de métodos analíticos Cromatografia Líquida de Alta Eficiência Balanço de massa Degradação forçada espetroscopia FTIR-ATR