Determination of Sulfonamide Antibiotics in Environmental Aqueous Samples by Solid-Phase Extraction–Gel Permeation Chromatography Purification Coupled with Ultra-Performance Liquid Chromatography–Triple Quadrupole Mass Spectrometry

• • The combined SPE-GPC cleanup reduced matrix suppression, achieving LODs of 0.7–4.4 ng·L−1 and LOQs of 2.8–17.6 ng·L−1, enabling trace-level detection in complex water matrices. • • Recoveries at three spiking levels (10, 200, 400 ng·L−1) ranged from 44.5%–115%, with RSDs below 10% across all levels, demonstrating accuracy and precision suitable for regulatory monitoring. • • The method detected five sulfonamides in real samples at concentrations up to 3864 ng·L−1, confirming its applicability to surface water and wastewater effluent analysis. • • The use of Na2EDTA (2.5 mg·L−1) and pH adjustment to 6 were critical for chelating metal ions and optimizing extraction efficiency, addressing common pitfalls in antibiotic analysis.