A Sustainable Hybrid (NH ₄ ) ₂ SO₄‐Driven SALLE–Fluorimetric On–Off Integrated Platform for the Determination of Cinacalcet HCl: A Calcium Receptors Sensing Drug in Different Matrices

ABSTRACT A sustainable analytical platform was established through the combination of salting‐out assisted liquid–liquid extraction (SALLE) with fluorescence quenching for the trace‐level quantification of cinacalcet hydrochloride (CC•HCl). Ammonium sulfate (approved as a safe food additive) was utilized as the phase‐separating reagent, whereas eosin Y (EY), a biologically safe fluorescent dye, was selected as the sensing probe. Under acetate buffer conditions (pH 4.6), a stable, nonfluorescent ion pair complex was formed between CC•HCl and EY, producing concentration‐dependent quenching responses ( λ em = 555 nm). A linear working range of 0.06–1.10 μg/mL was obtained ( r = 0.9998), with detection and quantitation limits reaching 0.0166 and 0.0503 μg/mL, respectively. Full validation was carried out per ICH Q2(R1) guidelines, confirming acceptable accuracy, specificity, and precision. Kinetic characterization was performed through Stern–Volmer modeling ( K SV = 29.13 × 10 12 L·mol −1 ·s −1 and dissociation constant, K d = 6.90 × 10 −6 M), double logarithmic plots (association constant, K a = 1.45 × 10 5 L·mol −1 ), Scatchard analysis ( K (Scatchard) = 4.32 × 10 5 M −1 ), and the Langmuir adsorption isotherm ( K (Langmuir) = 8.51 × 10 4 ng/mL), all of which verified a specific, high‐affinity drug–probe interaction. The platform was further applied to tablet uniformity testing and CC•HCl determination in human biological fluids.