Modern Sample Pretreatment Approaches for β-Lactam Antibiotics in Complex Matrices: Challenges and Innovations

β-lactam antibiotics, widely used in human and veterinary medicine, can trigger serious public health concerns through misuse-including antimicrobial resistance and drug residues. The detection of β-lactam antibiotics faces three challenges: unstable β-lactam rings prone to hydrolysis, complex metabolism requiring multi-residue analysis, and trace-level concentrations (μg/kg) with severe matrix interference demanding high sensitivity and accuracy. Thus, systematically optimizing sample analytical methods is essential to enhance monitoring programs and ensure food safety. This review offers a comprehensive overview of contemporary pretreatment methodologies, encompassing well-established techniques such as solid-phase extraction and dispersive liquid-liquid microextraction, as well as innovative approaches including solidification floating organic droplet liquid-liquid microextraction and electromembrane extraction. Recent advancements in pretreatment strategies for β-lactam antibiotics are increasingly oriented toward achieving high extraction and purification efficiency, enhancing environmental sustainability, and improving the reusability of extraction materials. By critically evaluating the advantages and limitations of various techniques, this review aims to support progress in detection accuracy and reliability, increase analytical throughput and efficiency, and reduce operational costs.