This work represents the first successful application of a molecularly imprinted polymer (MIP)-based electrochemical sensor for the sensitive and selective determination of the first developed proteasome inhibitor, bortezomib (BOR). BOR is used for the treatment of multiple myeloma, gastrointestinal stromal tumors, and mantle cell lymphoma. It shows its desired effect through the boronate group and can be administered intravenously or subcutaneously. The MIP-based electrochemical sensor design includes the integration of green-synthesized saffron-based copper nanoflowers (CuNFs) from Crocus sativus L. to increase the active surface area and porosity of the glassy carbon electrode (GCE) surface. 2-Acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was selected as the functional monomer along with other MIP components. Detailed characterizations of the developed CuNFs/AMPS/MIP-GCE sensor and CuNFs were performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDX), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The indirect measurement approach using 5.0 mM [Fe(CN)6]3–/4– solution was used to determine BOR in the linear range of 2.5 × 10−13 M − 2.5 × 10−12 M (0.25–2.5 pM). The LOD and LOQ values of the sensor obtained at the fM level (29 fM and 96.7 fM), which has a linear response in the commercial human serum sample in the same concentration range, emphasize its sensitivity (1.89 × 1013 and 2.14 × 1013 μA/M for standard solution and serum). The repeatability and reproducibility of the sensor were between 0.87 % and 2.17 %, showing its reliability. The successful performance of the sensor in the presence of metabolites belonging to BOR demonstrates its unique selectivity. The selectivity was demonstrated via relative imprinting factor (IF') values (higher than 3.5) against BOR's metabolites. The stability of the CuNFs/AMPS/MIP-GCE sensor was found to be 5 days.
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