Abstract The accurate determination of clozapine (CLZ), an essential antipsychotic drug, remains challenging due to complex pharmaceutical matrices and the need for high sensitivity. Conventional methods like HPLC and UV-Vis are limited by time-consuming procedures and unsuitability for on-site analysis. To address this, a novel hybrid nanocomposite based on a chitosan Schiff base functionalized with 2-(2-acetamidophenyl)-2-oxoacetic acid (Chs-KA), β-cyclodextrin (β-CD), and zinc oxide nanoparticles (ZnO NPs) was successfully synthesized. Structural characterization confirmed the formation of the Chs-KA Schiff base via imine linkage (FTIR band at ~ 1640 cm⁻¹), while XRD analysis revealed the incorporation of crystalline ZnO with a wurtzite structure and an average crystallite size of 8–20 nm. This composite was employed to fabricate a modified carbon paste electrode (Chs-KA/β-CD/ZnO NPs/CPE) for the sensitive detection CLZ. The sensor demonstrated a proton-coupled electron transfer mechanism (slope of − 47 mV/pH) with adsorption-controlled kinetics (heterogeneous electron transfer rate constant, ks = 2.67 s⁻¹). Under optimized conditions, the electrode exhibited a wide linear response range from 0.5 nM to 7.0 µM, a very low detection limit of 0.13 nM, and high selectivity against common interferents (signal change < 5%). The sensor showed excellent reproducibility (RSD = 2.05%) and retained 95.64% of its initial response after one month. Practical applicability was validated by determining CLZ in commercial tablet formulations, with recovery rates ranging from 97.0% to 102.0%. This work provides a powerful platform for pharmaceutical quality control and establishes a design strategy for advanced biopolymer-based electrochemical sensors. Future work includes application to other psychoactive drugs, biological fluid monitoring, and commercial scalability.
Taha et al. (Mon,) studied this question.