Validação de metodologia analítica por cromatografia liquida de alta eficiencia (CLAE), para determinação de mefloquina e carboximefloquina em amostras de sangue total adsorvidas em papel de filtro, em pacientes com malária por Plasmodium falciparum
Among the main challenges for malaria control in Brazil and in the world, the advent of resistance to the Plasmodium, particularly Plasmodium falciparum, is presented as the most relevant. Mefloquine is a drug of first line for the treatment of falciparum malaria, and the availability of sensitiv...
| Autor principal: | ATAIDE, Patrícia Marques de |
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| Grau: | Dissertação |
| Idioma: | por |
| Publicado em: |
Universidade Federal do Pará
2013
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| Assuntos: | |
| Acesso em linha: |
http://repositorio.ufpa.br/jspui/handle/2011/3892 |
| Resumo: |
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Among the main challenges for malaria control in Brazil and in the world, the advent of
resistance to the Plasmodium, particularly Plasmodium falciparum, is presented as the most
relevant. Mefloquine is a drug of first line for the treatment of falciparum malaria, and the
availability of sensitive methods and low cost for monitoring of blood concentrations of the
drug and carboxymefloquine assists in the optimization of drug regimens. In this sense,
analytical methodology was validated in accordance with the parameters suggested by official
regulatory agency for determination of mefloquine and its carboxylated derivative on the
whole blood sample adsorbed on filter paper. The method was employed using High
Performance Liquid Chromatography after liquid-liquid extraction of the analytes. The
detection was performed at 222nm. No interference was observed in other antimalarials
commonly used. The method was linear in concentration range from 0.25 to 2.5 μg/mL for
mefloquine and its carboxylated derivative. The detection and quantification limits were 35
ng/mL and 70 ng/mL for mefloquine and carboxymefloquine, respectively. The average intra
assay precision was 31±4% for mefloquine and 21±5% for carboxymefloquine. The average
inter assay precision was 38±4% for mefloquine and 25±7% for carboxymefloquine. The
average of recovery for concentrations of mefloquine ranging from 0.25 to 2.5μg/mL was
83±14% and carboxymefloquine varying from 0.375 to 3740 μg/mL was 88±11%. The drug
was stable in samples adsorbed on filter paper for a period of a month. . The method showed
to be robust for small changes on pH of the mobile phase. To evaluate the applicability of the
method was performed determination of analytes in blood samples adsorbed on filter paper
from patients with falciparum malaria. The average concentration of mefloquine was
0.861±0.723 μg/mL and carboxymefloquine 0.472±0.086 μg/mL. The validation parameters
of the analytical methodology followed the recommendations proposed by the official
agencies and the method showed to be appropriate for determination of mefloquine and
carboxymefloquine in whole blood samples adsorbed on filter paper. |