Eco‐Friendly Spectrofluorimetric Method for Ranolazine Determination Using Erythrosin B Quenching: Central Composite Design Optimization and Application to Pharmaceutical and Plasma Analysis

A novel, sensitive, and eco‐friendly spectrofluorimetric method has been developed and validated for ranolazine determination in pharmaceutical formulations and human plasma samples. The method exploits the fluorescence quenching of erythrosin B upon interaction with ranolazine under optimized conditions. Central composite design was employed to systematically optimize critical experimental parameters, establishing optimal conditions at pH 6.0, erythrosin B concentration of 11 μg/mL, and a 4‐min reaction time. Mechanistic investigations through Stern–Volmer analysis revealed static quenching with temperature‐dependent quenching constants (2.05 × 10 5 M −1 at 298 K to 1.55 × 10 5 M −1 at 313 K), whereas Job's method confirmed 1:1 stoichiometry. The validated method exhibited excellent linearity (0.3–4.0 μg/mL, r 2 = 0.9996) with superior sensitivity (LOD = 0.083 μg/mL, LOQ = 0.251 μg/mL), high precision, and satisfactory accuracy (recovery = 99.25% ± 1.18%). Successful application to both pharmaceutical tablets and human plasma samples demonstrated excellent recoveries with statistical equivalence to an HPLC reference methodology. Environmental sustainability assessment using multiple green chemistry metrics (AGREE = 0.70, MoGAPI = 74%, BAGI = 77.5, RGB12 = 87.8%) confirmed superior ecological performance compared to conventional chromatographic approaches. The proposed method represents a sustainable, cost‐effective alternative for routine pharmaceutical quality control and therapeutic drug monitoring applications.