Recent Advances in Non-Enzymatic Electrochemical Sensors for Theophylline Detection

Detection of target analytes at low concentrations is significant in various fields, including pharmaceuticals, healthcare, and environmental protection. Theophylline (TP), a natural alkaloid used as a bronchodilator to treat respiratory disorders such as asthma, bronchitis, and emphysema, has a narrow therapeutic window with a safe plasma concentration ranging from 55.5–111.0 μmol·L–1 in adults. Accurate monitoring of TP levels is essential because too low or too high can cause serious side effects. In this regard, non-enzymatic electrochemical sensors offer a practical solution with rapidity, portability, and high sensitivity. This article aims to provide a comprehensive review of the recent developments of non-enzymatic electrochemical sensors for TP detection, highlighting the basic principles, electro-oxidation mechanisms, catalytic effects, and the role of modifying materials on electrode performance. Carbon-based electrodes such as glassy carbon electrodes (GCEs), carbon paste electrodes (CPEs), and carbon screen-printed electrodes (SPCEs) have become the primary choices for non-enzymatic sensors due to their chemical stability, low cost, and flexibility in modification. This article identifies the significant contribution of various modifying materials, including nanomaterials such as carbon nanotubes (CNTs), graphene, metal oxides, and multi-element nanocomposites. These modifications enhance sensors’ electron transfer, sensitivity, and selectivity in detecting TP at low concentrations in complex media such as blood plasma and pharmaceutical samples. The electro-oxidation mechanism of TP is also discussed in depth, emphasizing the hydroxyl and carbonyl reaction pathways strongly influenced by pH and electrode materials. These mechanisms guide the selection of the appropriate electrode material for a particular application. The main contribution of this article is to identify superior modifying materials that can improve the performance of non-enzymatic electrochemical sensors. In a recent study, the combination of multi-element nanocomposites based on titanium dioxide(TiO2), CNTs, and gold nanoparticles(AuNPs) resulted in the lowest detection limit of 3 × 10–5 μmol·L–1, reflecting the great potential of these materials for developing high-performance electrochemical sensors. The main conclusion of this article is the importance of a multidisciplinary approach in electrode material design to support the sensitivity and selectivity of TP detection. In addition, there is still a research gap in understanding TP’s more detailed oxidation mechanism, especially under pH variations and complex environments. Therefore, further research on electrode modification and analysis of the TP oxidation mechanism are urgently needed to improve the accuracy and stability of the sensor while expanding its applications in pharmaceutical monitoring and medical diagnostics. By integrating various innovative materials and technical approaches, this review is