Advanced hierarchical ZnFe-LDH@MnO₂ nanostructures for sensitive voltammetric determination of lenalidomide

The accurate determination of lenalidomide (LEN) is essential due to its widespread clinical use and narrow therapeutic window. In this context, a novel, eco-friendly electrochemical sensor based on a ZnFe-LDH@MnO₂ nanocomposite-modified glassy carbon electrode (ZnFe-LDH@MnO₂/GCE) was developed for the sensitive determination of LEN. The hybrid nanocomposite was synthesized via a rapid two-step procedure involving microwave-assisted formation of ZnFe-LDH followed by controlled MnO₂ deposition. Structural and physicochemical characterization using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, Field emission scanning electron microscopy/Energy dispersive X-ray spectroscopy (FE-SEM/EDX), Brunauer-Emmet-Teller (BET) analysis, and Thermogravimetric analysis (TGA) confirmed the successful formation of a hierarchically structured nanocomposite with a significantly increased surface area (113.88 m 2 /g for ZnFe-LDH@MnO₂ vs. 77.40 m 2 /g for ZnFe-LDH) and improved thermal stability. Electrochemical studies revealed enhanced electron-transfer kinetics, evidenced by a decrease in charge-transfer resistance (Rct) from 3218.7 Ω to 1050.1 Ω and an increase in electroactive surface area from 0.085 cm 2 to 0.14 cm 2 after modification. LEN exhibited an irreversible oxidation process involving a 2e⁻/1H⁺ mechanism, which was quantitatively monitored using differential pulse voltammetry (DPV). Under optimized conditions, the sensor demonstrated a wide linear range of 0.50–9.80 µM (R 2 = 0.995), with a low limit of detection (LOD) of 6.99 nM. The developed platform showed excellent repeatability (relative standard deviation, RSD = 1.1%) and reproducibility (RSD = 0.4%), along with high selectivity against common interfering species. Furthermore, the environmental impact of the method was evaluated using Green Analytical Procedure Index (GAPI), Analytical GREEnness (AGREE) (0.84), and Blue Applicability Grade Index (BAGI) (77.5) tools, confirming its sustainability and practical applicability. The sensor was successfully applied to human plasma, synthetic urine, and pharmaceutical dosage forms, yielding satisfactory recoveries (98.2%–101.7%). These results demonstrate that the proposed sensor provides a green, sensitive, and cost-effective alternative for routine LEN determination in clinical and pharmaceutical analysis.