This study synthesized and characterized layered double hydroxides (LDHs) intercalated with ethylenediaminetetraacetic acid (EDTA) to increase the basal spacing of electrosynthesized Zn-Al-LDHs on pencil graphite (PG). The characteristic verification of the Zn-Al-EDTA-LDH nanostructures was conducted utilizing Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive and X-ray analysis (EDS), and X-ray diffraction (XRD). To improve the extraction efficiency, Zn-Al-EDTA-LDHs as adsorbent in solid phase microextraction (SPME) fiber was combined with hollow fiber liquid–liquid phase microextraction (HF-LLPME) to investigate the extraction efficiency of HF-LLME@PG-SPME technique the chosen non-steroidal anti-inflammatory drugs (NSAIDs) from aqueous solution Several variables, comprising extraction time, desorption time, stirring rate, desorption volume, pH of donor phase, and salt effects were screened and optimized by performing placket-Burman design (PBD). After evaluating the extraction and desorption procedures under optimal conditions, NSAIDs analysis was performed employing high-performance liquid chromatography-ultraviolet detection (HPLC-UV). Compared to the most common clean-up and sample preparation methods, the current study focused on developing a greener analytical chemistry process due to reduced solvent consumption, cost-effectiveness, miniaturization and simplified design. The proposed method for NSAIDs exhibited a good linear dynamic range (LDRs) (1.00–200.00 µg/L) with a coefficient of determination of > 0.9956, low limits of detection (LODs) (0.26–0.29 µg/L) and acceptable limits of quantifications (LOQs) (0.86–0.96 µg/L). Relative standard deviations of 5.31 % could be determined. The absolute recoveries of the urine sample analyses could be obtained in a 89.91–97.61 % range and enrichment factors (EFs) (178.92 to 183.88). Investigations of the developed method were also conducted in various urine samples containing the selected drugs. As a result of the obtained recoveries, the method proved to be valuable and suitable to complicated biological samples.
