PET-modulated fluorescence enhancement of cabergoline: A DFT and time-resolved fluorescence guided analytical strategy.

A novel, green, and highly sensitive spectrofluorimetric approach for the determination of cabergoline (CG) is presented. The method relied on the strategic modulation of the photoinduced electron transfer (PET) process. The native fluorescence of CG is inherently decreased by its tertiary amine moiety. The addition of hydrochloric acid efficiently diminishes this PET pathway ("PET-off"), resulting in a considerable, acid-induced improvement of the intrinsic fluorescence signal at 330 nm (excitation at 280 nm). The suggested mechanism is verified by density functional theory (DFT) calculations, which show a reduced HOMO-LUMO energy gap upon protonation, and by time-resolved fluorescence measurements confirming a significant increase in fluorescence lifetime of the protonated CG. Furthermore, analysis of the electrostatic potential (ESP) maps offered visual evidence of the electronic redistribution upon protonation. Following systematic optimization, the method demonstrates excellent analytical performance for the standard CG quantification and spiked human plasma in the ranges of 25 - 500 and 40 - 400 ng/mL, respectively. The method was fully validated per ICH guidelines, showing high accuracy (recoveries: 98.50 - 100.51%) and precision (%RSD < 2.0%). The described method was successfully applied for the assay of CG in pharmaceutical tablets, with statistical comparison to a reference method, and to content uniformity testing per USP guidelines. The method also proved real feasibility for the determination of CG in spiked human plasma samples. A comprehensive green chemistry assessment using AGREE metric, BAGI metric, ComplexMoGAPI, as well as RGB model, supported the method's outstanding green environmental profile and sustainable practical applicability. This PET-based fluorimetric strategy offers a simple, rapid, eco-friendly, and cost-effective alternative for the routine analysis of CG in quality control and bioanalytical laboratories.