Labeling of alprenolol with fluorescent aryl iodide as a reagent based on Mizoroki–Heck coupling reaction

Abstract

A novel fluorescent labeling method for alprenolol was developed based on Mizoroki–Heck coupling reaction. We designed and synthesized fluorescent aryl iodide, 4-(4,5-diphenyl-1 H-imidazol-2-yl)iodobenzene (DIBI) as a labeling reagent. DIBI has a lophine skeleton carrying an iodide atom acting as fluorophore and reactive center, respectively. In order to evaluate the usefulness of DIBI, a high-performance liquid chromatography (HPLC) with fluorescence detection method was developed for the determination of alprenolol as a model compound of terminal double bond. The fluorescent labeling of alprenolol with DIBI was achieved in the presence of palladium acetate as a catalyst, and the labeled alprenolol was detected fluorometrically. In addition, it was found that the fluorescence of DIBI derivative increased and red shifted when compared with that of DIBI. Furthermore, the proposed method could be applied to determine the alprenolol concentration in rat plasma after administration of alprenolol without interferences from biological components. The detection limit (S/N = 3) for alprenolol in rat plasma was 0.74 ng/mL (30 fmol on column).