Metal–Sulfonamide Interactions as an Overlooked Factor in Analytical Monitoring and Degradation Studies

Sulfonamides as antibacterial drugs are widespread environmental contaminants, and their determination and removal assessment are complicated by trace-level occurrence, matrix effects, and transformation products. A largely overlooked source of uncertainty is their interaction with metal ions present in environmental matrices or introduced during treatment. This critical review evaluates strategies for sulfonamide monitoring and degradation analysis from a metal-induced speciation perspective, focusing on sample preparation, chromatographic and mass-spectrometric determination, high-resolution mass spectrometry for suspect and non-target screening, and emerging sensing platforms. Rather than treating metals solely as matrix constituents or process catalysts, we examine them as speciation-controlling agents that can alter extraction recovery, chromatographic behavior, ionization, adsorption, and apparent degradation kinetics. Metal ions can enhance sulfonamide retention through coordination-mediated bridging, modify sorbent properties, activate peroxide- and persulfate-based oxidants, and redistribute sulfonamides between phases, potentially altering physicochemical properties, biodegradability, toxicity, and transformation pathways. This may cause decreases in measured dissolved concentrations to be misinterpreted as degradation or removal. Key gaps include distinguishing free from metal-bound sulfonamides, assessing how complexation affects mass-spectrometric ionization and fragmentation, and integrating speciation analysis with transformation-product identification and toxicological assessment. Future studies should incorporate metal-sulfonamide interactions as an analytical variable to improve quantitative reliability, mechanistic interpretation, and environmental risk assessment.