Sensitive determination of amoxicillin in aqueous solution via Cu(II)-induced chelation and PEG 200-mediated fluorescence enhancement

Amoxicillin (AMX) exhibits intrinsically weak fluorescence due to its low quantum yield, limiting its direct fluorometric determination. In this study, a simple and sensitive fluorometric method for AMX detection in aqueous solution was developed based on the combined use of Cu(II) chelation and polyethylene glycol 200 (PEG 200) enhancement. The fluorescence intensity of AMX increased significantly upon coordination with Cu(II) ions, attributed to the formation of a rigid [Cu(AMX)2] complex that suppresses non-radiative decay. Kinetic analysis confirmed that the coordination reaction follows pseudo-first-order kinetics ((k = 0.0677 min−1, t1/2 = 10.24 min). Addition of 33% (v/v) PEG 200 further enhanced fluorescence intensity by through microenvironment modulation. Under optimized conditions (55 °C, pH 9.2, 40 min), the method exhibited a linear response in the range of 0.13–0.80 μmol·L−1, with a detection limit of 13.2 nmol·L−1 (S/N = 3) and relative standard deviation below 1.6% (n = 9). Furthermore, the method was successfully applied to the quantification of AMX in pharmaceutical preparations. This proposed method provides a cost-effective, environmentally friendly alternative to chromatographic methods for routine AMX analysis in pharmaceutical quality control.