Combination of on-chip electromembrane extraction and solid phase microextraction for determination of non-steroidal anti-inflammatory drugs from biological fluids using poly(methacrylic acid–ethylene glycol dimethacrylate)–Cu/Cr layered double hydro

In this study, an innovative combination of on-chip electromembrane extraction and solid-phase microextraction (EME-SPME) was proposed for the first time. To develop this system, a monolithic composite of poly(methacrylic acid-ethylene glycol dimethacrylate)-Cu/Cr layered double hydroxide was <i>in situ</i> synthesized in the acceptor channel. This microfluidic device was employed in the determination of non-steroidal anti-inflammatory drugs, including naproxen, diclofenac, and mefenamic acid, in human biological fluids. During the extraction procedure, the immigration of compounds driven by an electric field and subsequent adsorption into the solid phase were achieved simultaneously. Likewise, the desorption stage was performed subsequently, and an eluent was introduced into HPLC. Optimization of key parameters affecting the extraction efficiency of the analytes was performed to achieve the highest extraction efficiency. Under optimized conditions, the method demonstrated detection limits between 0.1 and 0.25 μg L^-1 for the target analytes. The obtained linearity was within the range of 0.5-500 μg L^-1 for naproxen and 1-250 μg L^-1 for diclofenac and mefenamic acid (<i>R</i>² ≥ 0.9962). The method provided acceptable precision (RSDs ≤ 8.1%) and notable extraction recoveries of 84.3-90.9%, corresponding to preconcentration factors of 56-61. The proposed method was applied to extract the target analytes from breast milk, urine, and plasma samples, yielding satisfactory results. Eventually, the employment of a sorbent in the acceptor phase with its macroporous monolithic structure and the integration of two methods were demonstrated to be beneficial to increase efficiencies based on the achieved results.