Microextraction by packed sorbent and high performance liquid chromatography for simultaneous determination of lumefantrine and desbutyl-lumefantrine in plasma samples

•A MEPS-HPLC method was developed for determination of lumefantrine and desbutyl-lumefantrine in plasma.•MEPS parameters were optimized using a factorial planning.•This simple and fast method was fully validated according to regulatory guidelines.•The concentration of the drug and its metabolite was monitored in blood samples from volunteers.•Desbutyl-lumefantrine was produced in a low rate in the blood. A bioanalytical method for the determination of lumefantrine and its metabolite desbutyl-lumefantrine in plasma samples using microextraction by packed sorbent (MEPS) and high-performance liquid chromatography was developed and validated. A complete factorial planning and surface response approach were employed to optimize the extraction parameters sample volume, dilution, aspirated sample volume and extraction cycles. The method employed C18 MEPS sorbent and diazepam as internal standard (IS). Separation was performed on a Luna C18 column (250 mm × 4.6 mm, 5 μm) at 35 °C, with mobile phase composed of acetonitrile and 0.05 % trifluoroacetic acid (68:32, v/v), detection at 305 nm and injection volume of 25 μL. The developed method showed to be selective, precise, accurate and linear in the range of 50–5000 ng/mL for lumefantrine and desbutyl-lumefantrine. Using the optimized MEPS procedure, high recovery rates were obtained for both analytes and IS (92.2 %–99.0 %). The method was successfully applied for the determination of lumefantrine and its metabolite in human plasma samples after oral administration of lumefantrine tablets in healthy volunteers.