Novel green-emissive carbon dots as a dual-purpose fluorometric tool for sensitive vismodegib detection and...

Accurate determination of vismodegib (VISMO), a Hedgehog pathway inhibitor approved for the management of basal cell carcinoma and other malignancies, is essential for pharmacokinetic assessment, dose optimization, and therapeutic drug monitoring. In this work, a novel green-emitting "turn-off" fluorometric probe based on nitrogen-doped carbon dots (G-N@CDs) was designed and optimized for the ultrasensitive and selective determination of VISMO in biological matrices. The fluorescence quenching behavior of the probe was predominantly governed by a synergistic combination of the inner filter effect and static quenching mechanisms, indicative of strong ground-state complexation between VISMO and surface functional groups of the G-N@CDs. Under optimized conditions, the system exhibited a broad dynamic linear response from 0 to 340 µM, with an exceptionally low detection limit of 0.4 nM (S/N = 3). The probe demonstrated a rapid signal response within one minute, outstanding selectivity against structurally related antineoplastic agents and common biological interferents, and excellent analytical precision with recoveries ranging from 97.6% to 103.5% and RSD values below 3.69%. Validation in human serum and urine samples confirmed the method's applicability for real-sample analysis, showing excellent agreement with UPLC results. The proposed G-N@CDs system was further employed for pharmacokinetic profiling of VISMO following oral administration, providing accurate concentration-time data that underscore its potential as a robust and cost-effective alternative to conventional chromatographic assays.