Recent advances in sample preparation for analysis of small molecules with surface-assisted laser desorption/ionization time-of-flight mass spectrometry: enrichment methods and applications

The detection of small molecules, including metabolites, pollutants, and drugs, is significant for clinical diagnosis, environmental monitoring, and drug analysis. Surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS), which integrates sample preparation and detection in one step, has attracted considerable attention in the analysis of small molecules. In SALDI-TOF MS, sample preparation is a key step to ensure analytical selectivity and sensitivity; however only a few relevant reviews summarize sample preparation. This paper reviews the recent progress of research on targeted and non-targeted enrichment methods for small molecular analytes in complex samples based on the SALDI-TOF MS platform, and discusses their applications in pollutant analysis, in vitro diagnosis, and drug analysis. Finally, the review can potentially inspire researchers to design and select suitable sample preparation methods to solve the challenges of background interference in complex analytical samples, thereby facilitating the development of new platforms for high-throughput and high-sensitivity detection.