Terbium-modified poly(diphenylamine orange) sensor enabling sustainable monitoring of imatinib: Voltammetric and DFT insights.

Therapeutic drug monitoring (TDM) of imatinib (IMB), a first-line tyrosine kinase inhibitor, is clinically essential due to its narrow therapeutic window and significant inter-individual pharmacokinetic variability. Existing analytical methods for IMB quantification suffer from limitations including high operational costs, complex sample preparation, toxicity concerns (mercury-based electrodes), and time-consuming procedures. This study describes the first-ever fabrication and application of a novel electrochemical sensor based on a terbium-modified polymerized diphenylamine orange composite on a pencil graphite electrode (Tb@poly-DPO/PGE) for sensitive, selective, and sustainable determination of IMB. The Tb@poly-DPO/PGE sensor was fabricated via sequential electropolymerization of DPO onto PGE followed by electrodeposition of Tb ions. The sensor was characterized using scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The Tb@poly-DPO/PGE sensor exhibited superior electrochemical performance with significantly enhanced electroactive surface area (0.175 cm2) and reduced charge-transfer resistance (112.0 Ω). Density functional theory (DFT) calculations were employed to investigate molecular-level interactions. A square-wave voltammetric (SWV) method was developed and validated according to ICH and EMA guidelines for IMB quantification in bulk solutions and spiked human plasma samples. The SWV method demonstrated linear response in two concentration ranges (0.025-0.5 μM and 1.0-4.5 μM) with a detection limit of 5.46 nM. The method showed acceptable trueness (recovery: 99.91-100.46%), precision (RSD ≤ 1.14%), selectivity, and stability over 20 days. Successful application to spiked human plasma samples demonstrated minimal matrix effects. The proposed method demonstrated superior analytical throughput (15 samples/hour in batch mode) and sustainability, achieving an Environmental, Performance, and Practicality Index score of 78.2. The fabricated sensor provides a robust, environmentally sustainable, and practically feasible platform for routine TDM of IMB, offering a promising alternative to existing analytical methodologies pending further validation on authentic patient samples.