Desenvolvimento de novas estratégias analíticas para determinação de lumefantrina em comprimidos e em amostra biológica

• Ano de defesa: 2019
• Autor(a) principal: Sarah Aparecida Siqueira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; FARMACIA - FACULDADE DE FARMACIA; Programa de Pós-Graduação em Ciências Farmacêuticas; UFMG
• Palavras-chave em Português: Malária; Lumefantrina; Cromatografia quiral; Desbutil-lumefantrina; Microextração em sorvente empacotado; Validação; Planejamento fatorial
• Link de acesso: http://hdl.handle.net/1843/33784

Malaria is a parasitic disease that represents a major public health problem in Africa, Asia and South America, with a high incidence worldwide. The management of the disease involves prophylaxis and drug treatment with associated drugs, among which artemether-lumefantrine is the first line treatment for falciparum malaria. Lumefantrine is a chiral drug presenting two enantiomers; however, it is marketed as racemate. The enantioselectivity of antimalarial drugs is evidenced by the incidence of adverse effects and the distinct susceptibility of Plasmodium to the enantiomers. Thus, evaluating lumefantrine enantioselectivity and properly quantifying its enantiomers is essential for a deeper understanding of the impact of this enantioselectivity in its pharmacodynamic and pharmacokinetic properties. For this, a chiral chromatographic method was developed and validated for the separation of lumefantrine enantiomers, using a Chiralpack AD-H column (150 x 4.6 mm, 5 μm), at 25 °C, mobile phase composed of hexane and isopropanol (97:3), flow rate of 1.0 mL/min and detection at 335 nm. The method was validated according to RDC nº 166/2017 from ANVISA, for linearity, precision, accuracy, selectivity and robustness. Within other scope, therapeutic monitoring of antimalarials through the quantification of plasmatic concentrations by sensitive and innovative bioanalytical methods is also an important tool to evaluate clinical efficacy and development of resistance to these drugs. Thus, a bioanalytical method was developed and validated for determination of lumefantrine and its metabolite, desbutyl-lumefantrine, in human plasma. Microextraction by packed sorbent (MEPS) was employed for sample preparation, with 250 µL syringe and C18 sorbent. Parameters used in sample preparation were optimized by factorial design. Chromatographic separation was performed in a Luna C18 column (250 x 4.6 mm, 5 µm), at 35 °C, acetonitrile and 0.05% trifluoroacetic acid (68:32) as mobile phase, flow rate of 1.0 mL/min and detection at 305 nm, with diazepam as internal standard. The method was validated according to RDC nº 27/2012 from ANVISA. Both developed methods showed to be adequate for separation and quantitation of lumefantrine. Therefore, new analytical approaches were available, and may be used in future studies for chiral evaluation or therapeutic drug monitoring.