Copper-chelation-induced ratiometric fluorescence response for sensitive ratiometric detection of zoledronic acid: implications for monitoring in renal impairment

Zoledronic acid (ZOL) is a potent bisphosphonate widely used in the treatment of bone disorders, including osteoporosis, Paget's disease, and bone metastases. Despite its clinical importance, current methods for ZOL detection in biological samples often require complex instrumentation and lengthy procedures. This study presents the first ratiometric fluorometric sensor for ZOL detection in real biological samples utilizing a dual emission carbon dots (D@CDs)/Cu ²⁺ system. The sensing mechanism relies on ZOL's strong affinity for copper ions. When ZOL is introduced into the D@CDs/Cu2 ⁺ system, it forms stable complexes with Cu2 ⁺, causing a measurable decrease in fluorescence emission at 370 nm while simultaneously enhancing emission at 578 nm. This dual-wavelength response enables highly sensitive ratiometric detection of ZOL. Comprehensive characterization of the D@CDs and the detection mechanism was conducted using various spectroscopic and analytical techniques. The developed method demonstrates excellent analytical performance with a wide linear detection range (10.0–90.0 nM) and strong correlation (R ² = 0.9949). The system achieves a remarkably low limit of detection (2.15 nM), making it suitable for measuring ZOL concentrations in biological fluids at clinically relevant levels. The practical utility of this method was validated through successful application to rat serum samples. Furthermore, the technique was employed to monitor ZOL levels in both healthy rats and those with experimentally induced renal dysfunction, enabling comparative pharmacokinetic analysis between these groups. The method's sensitivity and reliability make it a valuable tool for pharmacokinetic studies and therapeutic drug monitoring of ZOL in clinical applications.