Ultrasensitive, green molecularly-imprinted poly(o-phenylenediamine) sensor on pencil graphite for trace ertugliflozin quantification in plasma and tablets

This study presents an ultrasensitive electrochemical sensor aimed at the detection and quantification of ertugliflozin L-pyroglutamic acid (EGZ), an anti-diabetic agent, using molecularly imprinted polymer (MIP) technology. The sensor was fabricated by electropolymerizing o-phenylenediamine (o-PD) onto a pencil graphite electrode (PGE), with EGZ serving as the template molecule. The detection of EGZ was achieved through indirect sensing, where EGZ competes with the redox-active probe ferrocyanide/ferricyanide ([Fe (CN)₆]^3-/4-) for the binding sites of the MIP. The resulting electrical signal was measured using differential pulse voltammetry (DPV). The sensor demonstrated excellent sensitivity, with a linear response range from 1 × 10⁻¹² to 1 × 10⁻¹⁰ M and a limit of detection (LOD) of 6.3 × 10⁻¹⁴ M. A non-imprinted polymer (NIP) was prepared under the same electropolymerization conditions but without the inclusion of EGZ. The NIP sensor served as a control, and the imprinting factor (IF) was determined to be 6, confirming the success of the imprinting process and the formation of selective recognition sites. Characterization of the proposed sensor was conducted using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) coupled with energy-dispersive X-ray analysis (EDX). Additionally, the sensor successfully detected EGZ in spiked human plasma, demonstrating its practical applicability in complex biological samples. The environmental impact of the proposed method was assessed using the AGREE and GAPI green evaluation tools, which confirmed its environmentally friendly nature. Furthermore, the sensor exhibited high selectivity in the presence of commonly co-formulated drugs, such as sitagliptin and metformin, indicating its potential for pharmaceutical applications.