Development of an Electrochemical Platform Based on Zinc Oxide Nanoparticles Embedded onto Montmorillonite Clay Functionalized with Phenylalanine for the Nano-Sensing of Acetaminophen in Pharmaceutical Tablets

This study describes the development of an electrochemical sensor for quantitatively measuring acetaminophen (ACOP) in drug tablets. The sensor design is based on the modification of glassy carbon electrode (GCE) using zinc oxide nanoparticles (ZnONPs) embedded in a naturally occurring clay matrix (Sa) functionalized with phenylalanine (Phe). To ensure that the ZnONPs are homogeneously dispersed on the clay surface, the nanocomposite was synthesized using an impregnation approach and low-temperature heat treatment. The amino acid promotes specific interactions with ACOP through hydrogen bonding and π-π stacking, acting as both a stabilizing agent and a molecular recognition moiety. FTIR, UV-Vis, XRD, and FESEM/EDX mapping were employed to fully characterize the developed material (ZnONPs-Sa/Phe). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used for the electrochemical determination of ACOP using the modified electrode GCE/ZnONPs-Sa/Phe. Parameters susceptible to affecting the sensitivity of the developed sensor were optimized, revealing that 5 µL of the suspension ZnONPs-Sa/Phe immobilized on GCE was ideal for the sensing of ACOP in a phosphate buffer solution at pH 2.0. The calibration curve obtained by plotting peak current intensity against ACOP concentration exhibited linear behavior within the concentration range between 0.02 µM and 0.28 µM, enabling determination of the limits of detection (LOD) and quantitation (LOQ) at 8.54 × 10−9 M and 2.84 × 10−8 M, respectively. The reproducibility, stability, and selectivity of the sensor were evaluated, followed by its application to the nano-sensing of ACOP in Africure and Doliprane tablets, yielding satisfactory results. The simplicity, affordability, and high analytical sensitivity of the developed sensor make this sensing platform a promising tool for pharmaceutical quality control applications.