Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina
Ano de defesa: | 2013 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Minas Gerais
UFMG |
Programa de Pós-Graduação: |
Não Informado pela instituição
|
Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Link de acesso: | http://hdl.handle.net/1843/EMCO-9FRNKV |
Resumo: | Malaria is the most important parasitic disease in the world, placing it among the biggest challenges for the poorest countries in the area of health and development. It is estimated that in 2010 there were 216 million cases of malaria worldwide, with approximately 81% of cases in the African region. Also, it is estimated that there were 655,000 deaths, 91% of which occurred on the African continent. Approximately 86% of deaths were caused by malaria in children under 5 years of age. In Brazil, were reported to the Ministry of Health about 330,000 cases of the disease in 2010. In order to prolong the life cycle of the drug, particularly for delaying the onset of resistance, the treatment of malaria infection is performed using drug combinations. Moreover, it is necessary to monitor the plasma concentration of the drugs, correlating it with parasitemia. It is recommended, in the therapeutic manuals of malaria, combination therapy of artemisinin or its derivatives with other antimalarial drugs or antibiotics. In this study, we evaluated the combination of artesunate and mefloquine in salt form and the fixed-dose combination. Also, a bioanalytical method was developed and validated for the determination of artesunate, dihydroartemisinin (artesunate´s main metabolite) and mefloquine in human plasma. The salt artesunate mefloquine (MEFAS) was characterized as to its melting point, infrared spectrum and the chromatographic profile, with impurities that did not allow its use as pharmaceutical raw material. An analytical method for the determination of artesunate and mefloquine hydrochloride in fixed dose combination tablets was developed and validated. The parameters evaluated were selectivity, linearity, precision, accuracy and robustness, according to current legislation. We evaluated the stability of the solutions, which remained stable for at least 8 hours. Samples of four different batches of tablets were analyzed using the developed method and presented adequate drugs content. A bioanalytical method for the determination of artesunate, dihydroartemisinin (metabolite of artesunate) and mefloquine in plasma was developed and validated. The detection was performed using liquid chromatography tandem mass spectrometry. The method was validated according to current legislation. The parameters evaluated were selectivity, residual effect (carry over), matrix effect, linearity, precision, accuracy, and stability in biological matrix, after cycles of freezing and thawing, short term, post-processing and in solution. The bioanalytical method developed is adequate and can be used in studies of therapeutic drug monitoring. |
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Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquinaMétodo analíticoDiidroartemisininaPlasma humanoCLAECLAE-MSArtesunatoCloridrato de mefloquinaComprimidos em dose fixa combinadaValidação de métodoCromatografia líquida de alta eficiênciaTecnologia farmaceuticaEspectrometria de massaMaláriaFarmáciaAntimaláricosMalaria is the most important parasitic disease in the world, placing it among the biggest challenges for the poorest countries in the area of health and development. It is estimated that in 2010 there were 216 million cases of malaria worldwide, with approximately 81% of cases in the African region. Also, it is estimated that there were 655,000 deaths, 91% of which occurred on the African continent. Approximately 86% of deaths were caused by malaria in children under 5 years of age. In Brazil, were reported to the Ministry of Health about 330,000 cases of the disease in 2010. In order to prolong the life cycle of the drug, particularly for delaying the onset of resistance, the treatment of malaria infection is performed using drug combinations. Moreover, it is necessary to monitor the plasma concentration of the drugs, correlating it with parasitemia. It is recommended, in the therapeutic manuals of malaria, combination therapy of artemisinin or its derivatives with other antimalarial drugs or antibiotics. In this study, we evaluated the combination of artesunate and mefloquine in salt form and the fixed-dose combination. Also, a bioanalytical method was developed and validated for the determination of artesunate, dihydroartemisinin (artesunate´s main metabolite) and mefloquine in human plasma. The salt artesunate mefloquine (MEFAS) was characterized as to its melting point, infrared spectrum and the chromatographic profile, with impurities that did not allow its use as pharmaceutical raw material. An analytical method for the determination of artesunate and mefloquine hydrochloride in fixed dose combination tablets was developed and validated. The parameters evaluated were selectivity, linearity, precision, accuracy and robustness, according to current legislation. We evaluated the stability of the solutions, which remained stable for at least 8 hours. Samples of four different batches of tablets were analyzed using the developed method and presented adequate drugs content. A bioanalytical method for the determination of artesunate, dihydroartemisinin (metabolite of artesunate) and mefloquine in plasma was developed and validated. The detection was performed using liquid chromatography tandem mass spectrometry. The method was validated according to current legislation. The parameters evaluated were selectivity, residual effect (carry over), matrix effect, linearity, precision, accuracy, and stability in biological matrix, after cycles of freezing and thawing, short term, post-processing and in solution. The bioanalytical method developed is adequate and can be used in studies of therapeutic drug monitoring.A malária é a doença parasitária mais importante do mundo, posicionando-se entre os maiores desafios para os países mais pobres na área de saúde e desenvolvimento. Estima-se que, em 2010, houve 216 milhões de casos de malária no mundo, sendo aproximadamente 81% dos casos na região africana. Também, estima-se que houve 655000 mortes causadas pela doença, das quais 91% ocorreram no continente Africano. Aproximadamente 86% das mortes causadas por malária foram em crianças com menos de 5 anos de idade. No Brasil, foram relatados ao Ministério da Saúde aproximadamente 330 mil casos da doença em 2010. A fim de prolongar a vida útil dos medicamentos, principalmente para retardar o aparecimento de resistência, o tratamento da infecção malárica é realizado utilizando-se combinações de medicamentos. Além disso, é necessário monitorar a concentração plasmática dos fármacos, correlacionando-a com a parasitemia. É recomendado, nos manuais de terapêutica da malária, a terapia combinada da artemisinina ou seus derivados com outros fármacos antimaláricos ou antibióticos. Neste estudo, foi avaliada a combinação entre artesunato e mefloquina na forma de sal e na em dose fixa combinada. Foi também desenvolvido e validado um método bioanalítico para a determinação de artesunato, diidroartemisinina (seu principal metabólito) e mefloquina em plasma humano. O sal artesunato de mefloquina (MEFAS) foi caracterizado quanto ao seu ponto de fusão, espectro na região do infravermelho e perfil cromatográfico, apresentando impurezas que não permitiram a sua utilização como matéria-prima farmacêutica. Um método analítico para a determinação de artesunato e cloridrato de mefloquina em comprimidos em dose fixa combinada foi desenvolvido e validado. Foram avaliados os parâmetros de seletividade, linearidade, precisão, exatidão e robustez, segundo a legislação vigente. Foi avaliada a estabilidade das soluções, sendo estas estáveis por, ao menos, 8 horas. Amostras de comprimidos de quatro lotes distintos foram analisadas utilizando-se o método desenvolvido e foram consideradas com teor de fármacos adequado. Um método bioanalítico para a determinação de artesunato, diidroartemisinina (metabólito do artesunato) e mefloquina em plasma foi desenvolvido e validado. Foi utilizada a espectrometria de massas acoplada à cromatografia a líquido para a detecção dos analitos. O método foi validado segundo a legislação vigente. Foram avaliados os parâmetros de seletividade, efeito residual (carry over), efeito matriz, linearidade, precisão, exatidão, e as estabilidades em matriz biológica, após ciclos de congelamento e descongelamento, de curta duração, pós-processamento e do analito e padrão interno em solução. O método bioanalítico desenvolvido se mostrou adequado, podendo ser utilizado em estudos de monitorização terapêutica.Universidade Federal de Minas GeraisUFMGRoberto PontaroloRenata Barbosa de OliveiraIsabela da Costa CesarNeila Marcia Silva BarcellosJosianne Nicacio SilveiraMaria Betania de FreitasFernando Henrique Andrade Nogueira2019-08-10T02:56:35Z2019-08-10T02:56:35Z2013-07-08info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/EMCO-9FRNKVinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2019-11-14T10:13:23Zoai:repositorio.ufmg.br:1843/EMCO-9FRNKVRepositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2019-11-14T10:13:23Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.none.fl_str_mv |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
title |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
spellingShingle |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina Fernando Henrique Andrade Nogueira Método analítico Diidroartemisinina Plasma humano CLAE CLAE-MS Artesunato Cloridrato de mefloquina Comprimidos em dose fixa combinada Validação de método Cromatografia líquida de alta eficiência Tecnologia farmaceutica Espectrometria de massa Malária Farmácia Antimaláricos |
title_short |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
title_full |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
title_fullStr |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
title_full_unstemmed |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
title_sort |
Desenvolvimento e validação de métodos analíticos para a quantificação dos antimaláricos artesunato e mefloquina |
author |
Fernando Henrique Andrade Nogueira |
author_facet |
Fernando Henrique Andrade Nogueira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Roberto Pontarolo Renata Barbosa de Oliveira Isabela da Costa Cesar Neila Marcia Silva Barcellos Josianne Nicacio Silveira Maria Betania de Freitas |
dc.contributor.author.fl_str_mv |
Fernando Henrique Andrade Nogueira |
dc.subject.por.fl_str_mv |
Método analítico Diidroartemisinina Plasma humano CLAE CLAE-MS Artesunato Cloridrato de mefloquina Comprimidos em dose fixa combinada Validação de método Cromatografia líquida de alta eficiência Tecnologia farmaceutica Espectrometria de massa Malária Farmácia Antimaláricos |
topic |
Método analítico Diidroartemisinina Plasma humano CLAE CLAE-MS Artesunato Cloridrato de mefloquina Comprimidos em dose fixa combinada Validação de método Cromatografia líquida de alta eficiência Tecnologia farmaceutica Espectrometria de massa Malária Farmácia Antimaláricos |
description |
Malaria is the most important parasitic disease in the world, placing it among the biggest challenges for the poorest countries in the area of health and development. It is estimated that in 2010 there were 216 million cases of malaria worldwide, with approximately 81% of cases in the African region. Also, it is estimated that there were 655,000 deaths, 91% of which occurred on the African continent. Approximately 86% of deaths were caused by malaria in children under 5 years of age. In Brazil, were reported to the Ministry of Health about 330,000 cases of the disease in 2010. In order to prolong the life cycle of the drug, particularly for delaying the onset of resistance, the treatment of malaria infection is performed using drug combinations. Moreover, it is necessary to monitor the plasma concentration of the drugs, correlating it with parasitemia. It is recommended, in the therapeutic manuals of malaria, combination therapy of artemisinin or its derivatives with other antimalarial drugs or antibiotics. In this study, we evaluated the combination of artesunate and mefloquine in salt form and the fixed-dose combination. Also, a bioanalytical method was developed and validated for the determination of artesunate, dihydroartemisinin (artesunate´s main metabolite) and mefloquine in human plasma. The salt artesunate mefloquine (MEFAS) was characterized as to its melting point, infrared spectrum and the chromatographic profile, with impurities that did not allow its use as pharmaceutical raw material. An analytical method for the determination of artesunate and mefloquine hydrochloride in fixed dose combination tablets was developed and validated. The parameters evaluated were selectivity, linearity, precision, accuracy and robustness, according to current legislation. We evaluated the stability of the solutions, which remained stable for at least 8 hours. Samples of four different batches of tablets were analyzed using the developed method and presented adequate drugs content. A bioanalytical method for the determination of artesunate, dihydroartemisinin (metabolite of artesunate) and mefloquine in plasma was developed and validated. The detection was performed using liquid chromatography tandem mass spectrometry. The method was validated according to current legislation. The parameters evaluated were selectivity, residual effect (carry over), matrix effect, linearity, precision, accuracy, and stability in biological matrix, after cycles of freezing and thawing, short term, post-processing and in solution. The bioanalytical method developed is adequate and can be used in studies of therapeutic drug monitoring. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-07-08 2019-08-10T02:56:35Z 2019-08-10T02:56:35Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
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http://hdl.handle.net/1843/EMCO-9FRNKV |
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http://hdl.handle.net/1843/EMCO-9FRNKV |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais UFMG |
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Universidade Federal de Minas Gerais UFMG |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
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repositorio@ufmg.br |
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