Inhibition of photoinduced electron transfer for sensitive and eco-friendly spectrofluorimetric determination of metoprolol using D-optimal experimental design

Photoinduced electron transfer (PET) represents a significant phenomenon in fluorescence spectroscopy with wide-ranging applications across analytical chemistry. This study presents a novel spectrofluorimetric method for metoprolol determination based on blocking the PET process originating from the unshared electron pair of the secondary amine group in metoprolol’s structure. Upon acidification, the PET process was effectively inhibited, resulting in substantial fluorescence enhancement. Critical experimental parameters were optimized using D-optimal design of experiment methodology, including acid type and volume, diluting solvent, and reaction time. Notably, acetic acid produced superior fluorescence intensity even in the presence of organic solvents. This systematic approach facilitated understanding of factor interactions, leading to method robustness and a five-fold increase in sensitivity. The validated method demonstrated excellent analytical performance according to ICH guidelines, with linearity across 10–250 ng/mL, satisfactory accuracy, precision, robustness, and selectivity. Practical applicability was confirmed through successful analysis of pharmaceutical formulations and spiked plasma samples. Statistical comparison with a reference HPLC method revealed no significant differences in results. Environmental assessment using AGREE, BAGI, and RGB 12 metrics demonstrated the superior greenness and overall whiteness of the spectrofluorimetric method while maintaining comparable analytical practicality to the HPLC reference. This research elucidates the PET process in a widely prescribed cardiovascular drug, resulting in a rapid, cost-effective, and environmentally benign analytical method suitable for implementation in both quality control laboratories and clinical settings. The findings contribute to the growing field of sustainable analytical methodologies based on fundamental photochemical principles.