Desenvolvimento de métodos analíticos quirais para quantificação dos enantiômeros da cloroquina em comprimidos e em plasma humano
Ano de defesa: | 2017 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Minas Gerais
UFMG |
Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
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Palavras-chave em Português: | |
Link de acesso: | http://hdl.handle.net/1843/BUOS-BAVJMW |
Resumo: | Malaria is a disease with high epidemic potential, representing a serious public health problem in the world. In Brazil, chloroquine is the drug of first choice for the treatment of malaria caused by Plasmodium vivax. Therefore, it is essential that drugs containing chloroquine have quality, safety and efficacy. Chloroquine, as well as several other antimalarials, is chiral and demonstrates enantioselective pharmacodynamic and pharmacokinetic properties in humans and animals, however, these drugs are administered as racemates. The knowledge of stereoselective aspects of these agents may be useful to better understand their mechanisms of action and to optimize their safety and/or clinical efficacy. In this study, a chiral analytical method for the quantification of chloroquine enantiomers, was developed using high performance liquid chromatography with ultraviolet detector (HPLC-UV). The chromatographic conditions were: chromatographic column Chirobiotic V® (100 x 2.1 mm, 5 m) maintained at 25 ° C, mobile phase containing methanol: acetic acid: triethylamine (100: 0,12: 0,12), flow of 1 mL / min, injection volume of 10 L and detection at 258 nm. The validation parameters evaluated according to the current legislation were: selectivity, linearity, precision, accuracy, limits of detection and quantification, and robustness. Additionally, in a partnership with Canberra University, the enantioseparation of chloroquine by HPLC-UV, using a stationary phase Chiralpak ID and different composition of mobile phases was evaluated. Later, in a partnership with the Institute of Pharmaceutical Sciences, the bioanalytical method was developed by HLPC coupled to sequential mass spectrometry (HPLC-MS/MS) in order to carry out the therapeutic monitoring of chloroquine enantiomers in human plasma in the future. The chiral analytical methods developed allowed the separation and quantification of chloroquine enantiomers in tablets available commercially in Brazil. |