Molecularly imprinted polymer for determination of lumefantrine in human plasma through chemometric-assisted solid-phase extraction and liquid chromatography

Pedro Henrique Reis da Silva; Melina Luiza Vieira Diniz; Gerson Antônio Pianetti; Isabela da Costa César; Maria Elisa Scarpelli Ribeiro E Silva; Roberto Fernando de Souza Freitas; Ricardo Geraldo de Sousa; Christian Fernandes

doi:10.1016/j.talanta.2018.02.090

Molecularly imprinted polymer for determination of lumefantrine in human plasma through chemometric-assisted solid-phase extraction and liquid chromatography

Talanta. 2018 Jul 1:184:173-183. doi: 10.1016/j.talanta.2018.02.090. Epub 2018 Feb 26.

Authors

Pedro Henrique Reis da Silva¹, Melina Luiza Vieira Diniz¹, Gerson Antônio Pianetti¹, Isabela da Costa César¹, Maria Elisa Scarpelli Ribeiro E Silva², Roberto Fernando de Souza Freitas², Ricardo Geraldo de Sousa², Christian Fernandes³

Affiliations

¹ Laboratório de Controle de Qualidade de Medicamentos e Cosméticos, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
² Laboratório de Ciência e Tecnologia de Polímeros, Departamento de Engenharia Química, Escola de Engenharia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
³ Laboratório de Controle de Qualidade de Medicamentos e Cosméticos, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil. Electronic address: cfernandes@farmacia.ufmg.br.

PMID: 29674030
DOI: 10.1016/j.talanta.2018.02.090

Abstract

Lumefantrine is the first-choice treatment of Falciparum uncomplicated malaria. Recent findings of resistance to lumefantrine has brought attention for the importance of therapeutic monitoring, since exposure to subtherapeutic doses of antimalarials after administration is a major cause of selection of resistant parasites. Therefore, this study focused on the development of innovative, selective, less expensive and stable molecularly imprinted polymers (MIPs) for solid-phase extraction (SPE) of lumefantrine from human plasma to be used in drug monitoring. Polymers were synthesized by precipitation polymerization and chemometric tools (Box-Behnken design and surface response methodology) were employed for rational optimization of synthetic parameters. Optimum conditions were achieved with 2-vinylpyridine as monomer, ethylene glycol dimethacrylate as crosslinker and toluene as porogen, at molar ratio of 1:6:30 of template/monomer/crosslinker and azo-bisisobutyronitrile as initiator at 65 °C. The MIP obtained was characterized and exhibited high thermal stability, adequate surface morphology and porosity characteristics and high binding properties, with high affinity (adsorption capacity of 977.83 μg g^-1) and selectivity (imprinting factor of 2.44; and selectivity factor of 1.48 and selectivity constant of 1.44 compared with halofantrine). Doehlert matrix and fractional designs were satisfactorily used for development and optimization of a MISPE-HPLC-UV method for determination of lumefantrine. The method fulfilled all validation parameters, with recoveries ranging from 83.68% to 85.42%, and was applied for quantitation of the drug in plasma from two healthy volunteers, with results of 1407.89 and 1271.35 ng mL^-1, respectively. Therefore, the MISPE-HPLC-UV method optimized through chemometrics provided a rapid, highly selective, less expensive and reproducible approach for lumefantrine drug monitoring.

Keywords: Chemometrics; Lumefantrine; Malaria; Molecularly imprinted polymer; Molecularly imprinted solid phase extraction.

MeSH terms

Chromatography, High Pressure Liquid
Ethanolamines / blood*
Fluorenes / blood*
Humans
Lumefantrine
Molecular Imprinting*
Solid Phase Extraction*
Spectrophotometry, Ultraviolet

Substances

Ethanolamines
Fluorenes
Lumefantrine