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-vynilpyridine as monomer, ethylene glycol dimethacrylate as crosslinker and toluene as porogen, at molar ratio of 1:6:30 of template/monomer/crosslinker and azo-bisisobutironitrile 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
Author keywords: Malaria, Lumefantrine, Molecularly imprinted polymer, Chemometrics, Molecularly imprinted solid phase extraction