The automation of traditional Chinese medicine (TCM) manufacturing has advanced process analysis from offline to online modes. However, most existing online analytical technologies rely on spectroscopic methods, which still face difficulties in accurately identifying and quantifying individual compounds. In this study, we established a quality control (QC) system utilizing paper spray ionization miniature mass spectrometry (mini-MS) to monitor TCM production processes. This approach enabled, for the first time, real-time online qualitative and quantitative assessment of specific components in herbal extracts using mini-MS without the need for chromatographic separation. The dynamic variation of alkaloid compounds in Aconiti Lateralis Radix Praeparata (Fuzi) during the decoction process served as a demonstration, alongside an exploration of the underlying principles of Fuzi compatibility. Moreover, the system demonstrated reliable performance during continuous pilot-scale extraction over several hours. This mini-MS–based online analytical platform holds great promise for expanding QC applications across diverse pharmaceutical manufacturing processes.
