Eco-Friendly Sample Preparation Trends for Exogenous Toxic Organic Compounds in Food: A Sustainable Perspective for LC-MS Analysis

Exogenous toxic compounds in foods, arising from agricultural practices, environmental contamination, industrial processing, and packaging migration, remain a major global concern for food safety. These contaminants include mycotoxins, veterinary drug residues, antibiotics, pesticides, per- and polyfluoroalkyl substances, heterocyclic aromatic amines, and polycyclic aromatic hydrocarbons, which have multiple adverse effects on human and animal health. The continued presence of these substances highlights the need for reliable exposure assessment, strengthened regulatory frameworks, and advanced analytical methodologies. Food matrices introduce variability in analytical performance, making sample preparation a critical and often limiting step. Conventional extraction techniques such as solid-phase extraction, liquid-liquid extraction, and Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) are still widely applied. Moreover, recent advances have highlighted sustainable alternatives aligned with the principles of green analytical chemistry. In this context, this review provides a comprehensive overview of recent advances (2020-2025) in environmentally friendly extraction techniques for determining exogenous toxic compounds in food samples analyzed by liquid chromatography coupled with mass spectrometry (LC-MS), including their sustainability. Special attention is given to the chemical nature and toxicological relevance of major exogenous organic contaminant families (specialized categories such as hormones and packaging-derived bisphenols were excluded due to distinct migration and metabolic pathways; however, these topics exceed the scope of this manuscript), the analytical challenges associated with different food matrices, and the evolution of extraction and cleanup techniques. Overall, this review integrates analytical robustness, matrix effects, and green metrics to support the development of reliable and more sustainable sample preparation strategies.