Efficient determination of ranitidine, famotidine, and cimetidine in environmental and biological matrices using a NH₂-bimetallic MIL-88(Fe/Ni)@SiO₂/Fe₃O₄ composite and dispersive micro solid-phase extraction.

The widespread use of gastrointestinal drugs like ranitidine, famotidine, and cimetidine has led to their emergence as persistent environmental contaminants, while their monitoring in biological fluids remains crucial for clinical toxicology. This study presents the development of a sensitive and efficient analytical method based on dispersive micro solid-phase extraction (d-μ-SPE) coupled with high-performance liquid chromatography-photodiode array detector (HPLC-DAD) for their determination. A novel magnetic adsorbent, NH₂-bimetallic MIL-88(Fe/Ni)@SiO₂/Fe₃O₄, was synthesized and characterized. The unique bimetallic system and amine functionalization of the metal-organic framework (MOF) provided specific interactions with the target analytes, while the silica shell ensured stability, and the magnetic core facilitated separation. The critical factors affecting the d-μ-SPE efficiency were optimized using a two-stage experimental design: a definitive screening design (DSD) identified pH, sorbent dose, desorption time, and solvent volume as significant, and a subsequent central composite design (CCD) modeled their quadratic effects. Under optimal conditions, the method demonstrated low limits of detection (0.02-0.07 ng mL⁻1), high enrichment factors (59.3-72.5), and good precision (RSD < 5%). The method was successfully applied to tap, river, and well water, as well as human urine samples, achieving excellent relative recovery rates (89.8-95.3%), even in samples from individuals who had ingested the drugs. The adsorbent could be reused for three cycles without significant loss in performance.