Anti-immune complex recognition elements in small-molecule analysis: Preparation, applications, and mechanisms.

The determination of small-molecule compounds (SMCs), including veterinary drugs, pesticides, and mycotoxins, in food and environmental matrices remains a critical challenge in analytical chemistry, often demanding detection methods with high sensitivity and reliability. Conventional immunoassays for SMCs are predominantly limited to competitive formats due to the low molecular weight and single-epitope nature of these compounds, which often results in modest sensitivity and linearity. Anti-immune complex (anti-IC) recognition elements specifically bind to neo-epitopes that are generated upon formation of the antigen-antibody complex and are absent from either component alone. This binding property overcomes the limitation that small molecules cannot be detected in a sandwich format, enabling noncompetitive immunoassays in food matrices and related samples with markedly enhanced analytical performance. This review systematically consolidates the principal strategies for generating anti-IC recognition elements, critically evaluates their integration across diverse detection platforms, and synthesizes current mechanistic insights into how these reagents recognize immune complexes. It serves as a comprehensive guide for their rational development and application in high-performance immunoassays for SMC monitoring.