Electrochemical sensing of promethazine: A critical review of detection strategies, sensor architectures, and analytical challenges.

Abstract

Promethazine (PMZ) is a widely used phenothiazine drug whose accurate determination is important in pharmaceutical quality control, clinical monitoring, forensic toxicology, food analysis, and environmental surveillance. Although chromatographic and spectrometric methods remain valuable for confirmatory analysis, their dependence on sophisticated instrumentation and extensive sample preparation has encouraged the development of faster electrochemical alternatives. This review critically evaluates PMZ electrochemical detection studies published from 2010 to 2026, covering voltammetric methods, direct electrocatalytic detection, molecularly imprinted and DNA-mediated recognition, adsorptive stripping, and extraction-integrated electroanalysis. Particular attention is given to the effects of nanostructured materials, conductive composites, porous interfaces, and recognition layers on analytical performance. Comparative analysis indicates that nanostructured electrodes generally enhance sensitivity and electron transfer, whereas molecularly imprinted and DNA-modified interfaces offer greater potential for selective recognition. However, important trade-offs remain because high-surface-area and adsorption-based platforms are susceptible to fouling, affinity-based sensors often require complex fabrication and regeneration, and ultra-low detection limits frequently depend on prolonged preconcentration or sample pretreatment. Major research gaps include inadequate discrimination from structurally related phenothiazines, limited validation in authentic complex samples, poor inter-electrode and batch-to-batch reproducibility, and insufficient assessment of robustness, operational stability, total assay time, and cost. Future research should prioritize matrix- and fouling-resistant interfaces, simplified scalable fabrication, rigorous validation, and integrated sample handling. Combining reproducible disposable electrodes with microfluidics, portable potentiostats, and connected readout systems may facilitate reliable field-deployable and point-of-care PMZ analysis.