Molecularly imprinted polymer-based electrochemical sensor for sensitive determination of ticagrelor using activated pencil graphite electrode aided by molecular docking insights

For the first time, an electrochemical sensor based on the molecular imprinting technique (MIT) was fabricated for the selective determination of ticagrelor (TICA), an antiplatelet drug. A pencil graphite electrode (PGE) was activated in ethanolic hydrochloric acid, achieving sensitivity comparable to reported nanoparticle-modified electrodes without requiring nanomaterial preparation. Molecularly imprinted polymer (MIP) was formed by electropolymerization of o -phenylenediamine (OPD) around the PGE, and the superior monomer was selected. Moreover, molecular docking analysis corroborated the practical observations, establishing OPD as the most suitable monomer for the MIP design. Key experimental parameters affecting sensor performance; including pH, buffer type, extraction solvent, washing time, rebinding time, and electrode type, were systematically optimized. The developed sensor enabled the indirect determination of TICA using differential pulse voltammetry (DPV), exhibiting a linear range of 0.05 to 0.11 pM (R 2 = 0.998), with a detection limit of 0.0057 pM and a quantitation limit of 0.0173 pM. Following a 90 mg oral dose, ticagrelor reaches a reported peak plasma concentration of about 529 ng/mL. The developed sensor in this study is capable of detecting concentrations far below this level, demonstrating sensitivity comparing with previously reported methods. The sensor demonstrated excellent recovery in pharmaceutical formulations and spiked plasma, along with high selectivity against common interferents such as ascorbic acid, uric acid, glucose, sucrose, lactose, and clopidogrel. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines, confirming its accuracy, precision, and applicability for routine TICA analysis. The Act/MIP-PGE sensor exhibited excellent reproducibility, characterized by a relative standard deviation (RSD) of 1.97% for three independent measurements. Furthermore, the sensor demonstrated high selectivity in the presence of various interfering compounds. The innovation resides in utilizing the readily accessible and efficient activated PGE platform to support a highly selective MIP layer, facilitating cost-effective, sensitive, and reproducible electrochemical detection of ticagrelor, with enhanced electrode surface properties relative to untreated graphite electrodes.