Development of terbium-based fluorescence probe for Vericiguat quantitation in tablets and human plasma through advanced computational approaches

Abstract

Spectrofluorimetric techniques utilizing lanthanide sensitization are gaining increasing attention both presently and are anticipated to continue in the future. A distinctive, stable Terbium-based fluorescence probe was established to quantify vericiguat (VER), a groundbreaking oral soluble guanylate cyclase (sGC) stimulator, in tablets and human plasma. Density functional theory (DFT) calculations were employed to understand the potential binding between Tb3+ and VER in water and elucidate the stability of the VER-Tb3+ complex. The calculated binding energy of [Tb (VER)2]3+ was (􀀀 442.61 kcal/mol), highlighting the robustness of Tb3+–N coordination bonds and affirming Tb3+’s affinity towards VER in water. A validated fluorescent probe was optimized to leverage VER’s capacity to sensitize Tb3+ fluorescence by transferring energy from VER to Tb3+. The fluorescence of the VER-Tb3+ complex was examined at excitation and emission wavelengths of 260 nm and 545 nm; respectively. The method being proposed showed effectiveness within a linear range from 0.10 to 5.00 μg/mL, with detection and quantification limits of 19 and 58 ng/ mL; respectively. The method’s selectivity was confirmed through the study of different interferents. Adhering to ICH guidelines, the analysis was validated and applied to quantitate VER in human plasma and its pharmaceutical formulation, as well as to assess the content uniformity of tablets.