Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD

Detalhes bibliográficos
Autor(a) principal: Paiva, Marcelo Vitor de
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFRN
Texto Completo: https://repositorio.ufrn.br/jspui/handle/123456789/13477
Resumo: Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 μm. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methods
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spelling Paiva, Marcelo Vitor dehttp://lattes.cnpq.br/6323471692543395http://lattes.cnpq.br/9657118649043311Gomes, Ana Paula Barretohttp://lattes.cnpq.br/1689823596741892Pianetti, Gerson Antoniohttp://lattes.cnpq.br/5212837629822557Aragão, Cícero Flávio Soares2014-12-17T14:16:30Z2013-05-092014-12-17T14:16:30Z2013-03-21PAIVA, Marcelo Vitor de. Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD. 2013. 105 f. Dissertação (Mestrado em Bioanálises e Medicamentos) - Universidade Federal do Rio Grande do Norte, Natal, 2013.https://repositorio.ufrn.br/jspui/handle/123456789/13477Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 μm. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methodsA tuberculose é uma doença grave, porém curável em praticamente 100% dos casos novos, desde que obedecidos os princípios da moderna quimioterapia. São considerados fármacos de 1ª linha no tratamento à tuberculose: isoniazida, pirazinamida, etambutol e rifampicina. De acordo com USP 33 - NF28 (2010) as análises cromatográficas para 3 dos 4 fármacos (isoniazida, pirazinamida e rifampicina) duram em média 15 minutos e mais 10 minutos para a obtenção do 4° fármaco (etambutol) utilizando outra coluna, com outra mistura de fase móvel, tornando esta aplicação na prática industrial desfavorável. Uma das alternativas é utilizar o CLUE, o qual baseia-se nos mesmos princípios da CLAE, porém utiliza fases estacionárias com partículas menores que 2 μm. Dessa forma pretende-se com o presente estudo desenvolver e validar novos métodos analíticos para determinação simultânea de tuberculostáticos por CLAE/DAD e CLUE/DAD. Para isto, foi realizado um screening analítico, o qual verificou que é necessário um gradiente de sistema de fase móvel A (tampão acetato:metanol 94:6 v/v) e B (tampão acetato:acetonitrila 55:45 v/v). Posteriormente, ao desenvolvimento e otimização do método em CLAE e CLUE com a obtenção dos valores de adequabilidade do sistema dentro dos limites de aceitações vigente para ambos as técnicas, as validações deram-se início. Soluções padrões e soluções testes dos comprimidos foram preparadas e injetadas no CLAE e CLUE, contendo isoniazida, pirazinamida, etambutol e rifampicina nas concentrações de 0,008, 0,043, 0,030 e 0,016 mg.mL-1, respectivamente. A validação dos métodos analíticos foram realizadas para: especificidade / seletividade, intervalos da curva analítica, linearidade, limite de detecção, limite de quantificação, exatidão, precisão (repetibilidade, precisão intermediária) e robustez. Os métodos foram adequados para determinação dos 4 fármacos separadamente sem interferência nos demais. Precisos, devido ao fato de que os métodos demonstraram que mesmo com variação de dias, além da repetibilidade, os valores ficaram dentro da faixa preconizada na legislação vigente. Lineares (R > 0,99), ou seja, os métodos foram capazes de demonstrar que os resultados obtidos eram diretamente proporcionais à concentração do analito na amostra, dentro de um intervalo especificado. Exatos, uma vez que os métodos foram capazes de apresentar valores de coeficiente de variação e porcentagem de recuperação dentro dos limites exigidos (98 a 102%). Os métodos mostraram LD e LQ com níveis baixos demonstrando que os métodos possuem elevada sensibilidade aos quarto fármacos. A robustez foi avaliada frente às alterações de temperatura e fluxo, onde os métodos demonstraram-se robustos apenas nas condições previamente estabelecidas de temperatura e fluxo, alterações bruscas podem acarretar influência nos resultados dos métodosapplication/pdfporUniversidade Federal do Rio Grande do NortePrograma de Pós-Graduação em Ciências FarmacêuticasUFRNBRBioanálises e MedicamentosIsoniazida. Pirazinamida. Etambutol. Rifampicina. Cromatografia Líquida de Alta Eficiência. Cromatografia Líquida de Ultra EficiênciaIsoniazid. Pyrazinamide. Ethambutol. Rifampicin. High Performance Liquid Chromatography. 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dc.title.por.fl_str_mv Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
title Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
spellingShingle Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
Paiva, Marcelo Vitor de
Isoniazida. Pirazinamida. Etambutol. Rifampicina. Cromatografia Líquida de Alta Eficiência. Cromatografia Líquida de Ultra Eficiência
Isoniazid. Pyrazinamide. Ethambutol. Rifampicin. High Performance Liquid Chromatography. Ultra Fast Liquid Chromatography
CNPQ::OUTROS
title_short Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
title_full Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
title_fullStr Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
title_full_unstemmed Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
title_sort Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD
author Paiva, Marcelo Vitor de
author_facet Paiva, Marcelo Vitor de
author_role author
dc.contributor.authorID.por.fl_str_mv
dc.contributor.authorLattes.por.fl_str_mv http://lattes.cnpq.br/6323471692543395
dc.contributor.advisorID.por.fl_str_mv
dc.contributor.advisorLattes.por.fl_str_mv http://lattes.cnpq.br/9657118649043311
dc.contributor.referees1.pt_BR.fl_str_mv Gomes, Ana Paula Barreto
dc.contributor.referees1ID.por.fl_str_mv
dc.contributor.referees1Lattes.por.fl_str_mv http://lattes.cnpq.br/1689823596741892
dc.contributor.referees2.pt_BR.fl_str_mv Pianetti, Gerson Antonio
dc.contributor.referees2ID.por.fl_str_mv
dc.contributor.referees2Lattes.por.fl_str_mv http://lattes.cnpq.br/5212837629822557
dc.contributor.author.fl_str_mv Paiva, Marcelo Vitor de
dc.contributor.advisor1.fl_str_mv Aragão, Cícero Flávio Soares
contributor_str_mv Aragão, Cícero Flávio Soares
dc.subject.por.fl_str_mv Isoniazida. Pirazinamida. Etambutol. Rifampicina. Cromatografia Líquida de Alta Eficiência. Cromatografia Líquida de Ultra Eficiência
topic Isoniazida. Pirazinamida. Etambutol. Rifampicina. Cromatografia Líquida de Alta Eficiência. Cromatografia Líquida de Ultra Eficiência
Isoniazid. Pyrazinamide. Ethambutol. Rifampicin. High Performance Liquid Chromatography. Ultra Fast Liquid Chromatography
CNPQ::OUTROS
dc.subject.eng.fl_str_mv Isoniazid. Pyrazinamide. Ethambutol. Rifampicin. High Performance Liquid Chromatography. Ultra Fast Liquid Chromatography
dc.subject.cnpq.fl_str_mv CNPQ::OUTROS
description Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 μm. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methods
publishDate 2013
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2014-12-17T14:16:30Z
dc.date.issued.fl_str_mv 2013-03-21
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dc.identifier.citation.fl_str_mv PAIVA, Marcelo Vitor de. Otimização e validação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD. 2013. 105 f. Dissertação (Mestrado em Bioanálises e Medicamentos) - Universidade Federal do Rio Grande do Norte, Natal, 2013.
dc.identifier.uri.fl_str_mv https://repositorio.ufrn.br/jspui/handle/123456789/13477
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