Analytical methods should be accurate and specific to measure plasma drug concentration. Nevertheless, current sample preparation techniques suffer from limitations, including matrix interference and intensive sample preparation. In this study, a novel technique was proposed for the synthesis of a molecularly imprinted polymer (MIP) on magnetic Fe3O4 nanoparticles (NPs) with uniform core-shell structure. The Fe3O4@MIPs NPs were then applied to separate and enrich an antiepileptic drug, levetiracetam, from human plasma. A computational approach was developed to screen the functional monomers and polymerization solvents to provide a suitable design for the synthesized MIP. Different analysis techniques and re-binding experiments were performed to characterize the Fe3O4@MIP NPs, as well as to identify optimal conditions for the extraction process. Adsorption isotherms were best fitted to the Langmuir model and adsorption kinetics were modeled with pseudo-second-order kinetics. The Fe3O4@MIP NPs showed reasonable adsorption capacity and improved imprinting efficiency. A validated colorimetric assay was introduced as a comparable method to a validated HPLC assay for the quantitation of levetiracetam in plasma in the range of 10-80 μg mL-1 after extraction. The results from the HPLC and colorimetric assays showed good precision (between 1.08% and 9.87%) and recoveries (between 94% and 106%) using the Fe3O4@MIP NPs. The limit of detection and limit of quantification were estimated to be 2.58 μg mL-1 and 7.81 μg mL-1, respectively for HPLC assay and 2.32 μg mL-1 and 7.02 μg mL-1, respectively for colorimetric assay. It is believed that synthesized Fe3O4@MIP NPs as a sample clean-up technique combined with the proposed assays can be used for determination of levetiracetam in plasma.
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