Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Talanta (Oxford), 2018-07, Vol.184, p.173-183

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •Innovative molecularly imprinted polymer for lumefantrine extraction was synthesized.•Characterization of the MIP showed adequate stability, morphology and selectivity.•Chemometric approach was used for optimization of a MISPE-HPLC-UV for lumefantrine.•A rapid bioanalytical method was validated for determination of lumefantrine in plasma.•The MISPE-HPLC-UV method was successfully applied for two healthy volunteers.