Abstract

Monitoring the kinetic changes of drugs and metabolites plays a crucial role in fundamental research, preclinical and clinical application. Raman spectroscopy (RS) is regarded as a fingerprinting technique that can reflect molecular structures but limited in applications due to poor sensitivity. Surface-enhanced Raman spectroscopy (SERS) significantly amplifies the detection sensitivity by plasmonic substrates, facilitating the identification and quantification of small molecules in biological samples, such as serum, urine, and living cells. This review will focus on advances in how SERS has been utilized to monitor the dynamic processes of small molecule drugs and metabolites in recent years. We first provide readers with a comprehensive overview of the mechanism and practical considerations of SERS, including enhancement theory, substrate design, sample pretreatment, molecule-substrate interactions and spectral analysis. Then we describe the latest advances in SERS for the detection and analysis of metabolites and drugs in cells, dynamic monitoring of drug in various biological matrices, and metabolic profiling for health assessment in biological fluids. We believe that high-performance SERS substrates, standardized technical regulations, and artificial intelligence spectral analysis will boost sensitive, accurate, reproducible, and universal molecular detection in the future. We hoped this review could inspire researchers working in related fields to better understand and utilize SERS for the analytical detection of drugs and metabolites.

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