An electrochemical sensor based on an in situ synthesized hydroxyapatite – copper oxide (HAp@CuO) nanohybrid was developed as an efficient electrocatalytic platform for the sensitive determination of piroxicam (PX). The nanohybrid was comprehensively characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The electrochemical performance of the HAp@CuO nanohybrid modified carbon paste electrode (HAp@CuO nanohybrid CPE) was evaluated using cyclic voltammetry and electroactive surface area calculations. Compared with the bare electrode, the modified electrode exhibited a significant enhancement in oxidation peak current along with a negative shift in peak potential, confirming its strong electrocatalytic activity toward PX oxidation. Key experimental parameters, including solution pH, modifier content, and scan rate, were systematically optimized using Box–Behnken design (BBD) and response surface methodology (RSM) based on square wave voltammetry measurements. Under optimized conditions, the sensor displayed a wide linear response range from 0.05 to 50.0 μM (R2 = 0.995). The limits of detection (LOD) and quantification (LOQ) were calculated to be 0.014±0.004 and 0.048 ± 0.0017 μM (LOD ± SD, LOQ ± SD; n = 3), respectively. The proposed sensor demonstrated satisfactory selectivity, repeatability, and long-term stability, and was successfully applied to the determination of PX in pharmaceutical formulations and human urine samples.
