Surface-enhanced Raman spectroscopy (SERS) technology, possessing extraordinary sensitivity and an outstanding ability to furnish molecular-level information, has emerged as a revolutionary technique within the domain of analytical chemistry. This review comprehensively and in-depthly investigates the application of SERS in the field of pharmaceutical analysis, encompassing detailed analyses in diverse aspects such as ingredient identification, quality control, mechanism of action, and efficacy evaluation. Firstly, we introduce the key aspects of SERS technology, including its working principle, substrate preparation methods, and crucial factors in the experimental design process. Subsequently, the specific application of SERS in drug ingredient analysis is elaborated in detail, emphasizing its capability to rapidly identify active ingredients in complex mixtures, particularly the significant advantages it exhibits when tracking low-concentration bioactive molecules. At the quality control level, the application of SERS can precisely identify illegal adulteration in regular drugs, effectively guaranteeing the quality and consistency of drugs. Additionally, SERS also demonstrates great potential in analyzing the mechanism of action of natural drugs. It can clearly disclose the interaction between drugs and organisms at the molecular level and evaluate the effect of drugs. Although SERS technology has manifested extremely significant application prospects in the field of drug research, its widespread implementation still encounters some challenges, including the standardization of substrates, the reproducibility of signals, and the complexity of data processing. The future development direction will concentrate on the innovative design of substrates, the automation of the analysis process, and the organic integration with other bioanalytical technologies to enhance its accuracy and practicability in pharmaceutical analysis. Through continuous technological innovation and interdisciplinary cooperation, SERS technology is anticipated to play a more crucial role in the research and development of drugs, further promoting the continuous growth and innovation of the drug industry. This article aims to provide researchers in related fields with a comprehensive perspective on the current application status and future development trend of SERS technology, and also offer scientific basis and technical support for drug quality control and new drug development.

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http://dx.doi.org/10.1007/s00604-025-07029-9DOI Listing

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