A novel NiCaAl-LDH@ND-COOH nanocomposite-modified electrode for highly sensitive and selective electrochemical detection of larotrectinib in pharmaceutical and biological samples.

A novel electrochemical sensor based on a glassy carbon electrode (GCE) modified with a NiCaAl layered double hydroxide with carboxyl-functionalized nanodiamonds (NiCaAl-LDH@ND-COOH) was developed for the first time to enable sensitive and selective detection of larotrectinib (LARO), the first selective pan-tropomyosin receptor kinase (TRK) inhibitor used clinically for cancer treatment. The nanocomposite was synthesized by integrating NiCaAl layered double hydroxide (LDH) with carboxyl-functionalized nanodiamonds (ND-COOH), resulting in enhanced electrocatalytic performance. The individual electrochemical properties of ND-COOH and NiCaAl-LDH were systematically evaluated and compared with those of the combined nanocomposite. ND-COOH contributed high surface area, low background current, and improved conductivity, while NiCaAl-LDH offered abundant redox-active sites and high ion-exchange capacity. The NiCaAl-LDH@ND-COOH nanocomposite exhibited a synergistic enhancement in electron transfer kinetics and surface activity, as evidenced by cyclic voltammetry and impedance studies. Under optimized conditions, the sensor displayed a wide linear detection range (1.0 to 16.37 µM) and a low detection limit of 4.36 nM. It also demonstrated excellent repeatability (RSD = 1.3%), reproducibility (RSD = 1.23%), and high selectivity against common interferents. Successful application to pharmaceutical formulations, serum, and urine samples confirmed its practicality, achieving recoveries between 96.7% and 102.6%. This work provides the first electrochemical sensing platform for LARO, offering a reliable and cost-effective tool for its monitoring in clinical and pharmaceutical settings.