Abstract
Sertraline (SRT) is a widely prescribed selective serotonin reuptake inhibitor used for the treatment of major depressive disorder, anxiety disorders, obsessive–compulsive disorder, and posttraumatic stress disorder. Accurate and sensitive determination of SRT is essential for therapeutic drug monitoring, dose optimization, pharmacokinetic studies, and the prevention of adverse effects associated with inappropriate drug exposure. In this study, a simple and sensitive electrochemical sensing platform was developed for the determination of SRT, achieving a detection limit at nanomolar levels. The sensor was fabricated by modifying the SPCE surface with feather‐like Au−Ag−CoO
x
‐based multicomponent composite materials, which provided an enhanced electroactive interface for SRT oxidation. The structural and morphological properties of the prepared material were characterized using SEM, XRD, and AFM, while its electrochemical performance was investigated by voltammetric techniques. The Au−Ag−CoO
x
/SPCE sensor exhibited a markedly enhanced oxidation signal for SRT relative to the bare SPCE, confirming the electrocatalytic contribution of the Au−Ag−CoO
x
surface architecture. Under optimized conditions, the proposed sensor showed a linear response across the two linear ranges, from 2.0 × 10
−7
to 2.0 × 10
−6
M and 2.0 × 10
−6
to 2.0 × 10
−4
M, with a detection limit of 6.1 × 10
−8
M. The sensor also exhibited good selectivity against the testing interfering species, along with excellent repeatability and reproducibility, with RSD values of 1.46% and 1.75%, respectively, and acceptable long‐term stability by retaining approximately 85% of its initial response after 30 days. The practical applicability of the method was demonstrated through the analysis of SRT in pharmaceutical tablets, human serum, and water samples, yielding recovery values of 98.71%–102.35%, 97.45%–104.29%, and 100.80%–104.00%, respectively. Overall, the developed Au−Ag−CoO
x
/SPCE platform offers a reliable, cost‐effective, and sensitive approach for SRT determination in pharmaceutical, biological, and environmental samples.