The globalization of the food supply chain presents complex challenges for safety assurance within a highly fragmented regulatory landscape. This review synthesizes the frameworks of eight influential jurisdictions—including the European Union (EU), the United States, China, and Codex Alimentarius—to evaluate how legal mandates function as regulatory drivers that guide the evolution of analytical chemistry. By examining legislation on Maximum Residue Limits (MRLs), positive list systems, and method validation guidelines (e.g., SANTE), we demonstrate that strict preventive controls have established chromatography coupled with tandem mass spectrometry (LC/GC-MS/MS) as the universal standard for multi-residue screening. We show that global regulatory fragmentation is not merely an administrative artifact, but is rooted in divergent toxicological philosophies and localized dietary exposure models. This regulatory heterogeneity requires analytical laboratories to adopt a posture of “defensive technological redundancy,” forcing them to continuously optimize targeted methods against the strictest global default limits (e.g., 0.01 mg/kg). We establish that this continuous methodological escalation for ultra-trace quantification has reached practical and operational limits. Consequently, we conclude that the future of food safety testing must transition from static target-list compliance toward adaptable, non-targeted chemical profiling using High-Resolution Mass Spectrometry (HRMS), enabling laboratories to proactively address emerging contaminants, food fraud, and the complexities of modern food matrices.
Guo et al. (Tue,) studied this question.