Kaiwen Zhang, Bin Li, Yanying Chen, Haoyu Mai, Chang‐Jiang‐Sheng Lai
Direct mass spectrometry has become an important analytical approach in traditional Chinese medicine (TCM) because it enables rapid, direct, and minimally destructive characterization with little or no chromatographic pretreatment. In current TCM research, Direct mass spectrometry has shown clear advantages in rapid fingerprinting, authenticity assessment, process monitoring, and spatial chemical analysis, particularly in applications that require high throughput and in situ detection. However, its broader use remains constrained by several unresolved issues, including matrix effects, signal instability, limited quantitative robustness, poor interlaboratory reproducibility, and the lack of standardized spectral annotation and dedicated databases. These limitations mean that, at present, Direct mass spectrometry is more established for rapid qualitative assessment than for absolute quantification, cross-study comparison, and mechanism-related analysis. This review summarizes the major direct mass spectrometry platforms, their analytical principles, and their applications to different TCM analytical tasks and constituent classes, drawing mainly on representative studies from the past decade and including earlier foundational and early TCM-related reports where needed. It further highlights a central challenge in the field, namely the gap between rapid signal acquisition and reliable analytical interpretation, which continues to limit the extension of direct mass spectrometry from rapid screening to more robust practical application. Future progress will depend on methodological standardization, improved quantitative correction, stronger database support, and multimodal validation. Portable platforms and AI-assisted data analysis may further support field deployment and evidence interpretation when integrated into standardized and chemically interpretable workflows, thereby enabling direct mass spectrometry to play a more substantial role in TCM quality evaluation, process studies, and mechanism-related research.