The automation of traditional Chinese medicine (TCM) pharmaceuticals has driven the development of process analysis from offline to online. Most of common online process analytical technologies are based on spectroscopy, making the identification and quantification of specific ingredients still a challenge. Herein, we developed a quality control (QC) system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry (mini-MS). It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time. Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata (Fuzi) during decoction were used as examples, and the scientific principle of Fuzi compatibility was also investigated. Finally, the system was verified to work stably at the hourly level for pilot-scale extraction. This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

The quality of Chinese herbal medicine (CHM) raw materials is essential, and mass spectrometry (MS)-based technologies have been playing key roles in the quality control of CHMs. However, the use of miniature mass spectrometry (mini-MS) for quality control of CHMs has rarely been reported. In this work, we developed a rapid analytical method for the quality evaluation of CHMs based on paper spray ionization (PSI)-mini-MS/MS. The quality evaluation of Lygodium japonicum (Thunb.) Sw. was used as an example. Following a "multi-component" quality evaluation strategy, nine active constituents of L. japonicum were selected to be used as analytes for quality control. We confirmed that the precursor-product ion information in the MS/MS spectra of each analyte in the herbal extracts was consistent with the standards. Also, we developed a mini-MS-based quantitative method for each analyte using its quantification ion. The quantitative methodology was rigorously validated using quality control samples. Finally, the quality evaluation of L. japonicum was carried out using the established MS/MS method combined with statistical analysis. A wide range of common quality issues with L. japonicum can be effectively determined, including whether it is adulterated with sand and distinguishing among different parts and species. This study demonstrates that mini-MS for quality evaluation of CHMs is feasible. Mini-MS for quality evaluation of herbal medicines will potentially have a good prospect due to its many advantages such as low cost, low power consumption, and portability in the future.

Comprehensive chemistry experiments are very important to improve the overall quality of students, and to cultivate practical ability and innovation ability. This paper designs a comprehensive chemistry experiment. The experiment involved the extraction of crude berberine hydrochloride（BBH） from Berberis pliretii Schneid, recrystallization for purification, and qualitative and quantitative analysis of purified BBH using the Brick-L miniature mass spectrometry（mini-MS）. It can help undergraduate students better get in touch with the frontiers of analytical chemistry and develop students’ ability to analyze and solve chemical problems.

Interdisciplinary experiments within chemistry are very important for the improvements in the overall quality of the education received by students. In this work, we describe an interdisciplinary experiment that was successfully completed by undergraduate students. This training integrates multiple disciplines including natural product medicinal chemistry, organic synthesis, and instrumental analysis. The experiment involved the extraction of crude berberine hydrochloride (BBH) from Coptidis rhizoma, recrystallization for purification, and qualitative and quantitative analysis of purified BBH using the "Brick-L" miniature mass spectrometer (mini-MS). The use of mini-MS analysis is the highlight of this work. Mini-MS offers an unprecedented opportunity to incorporate MS analysis into regular undergraduate teaching due to its small size, low power consumption, and portability. The modular design of the mini-MS instrument used in this work allows instructors to disassemble the instrument on-site in the laboratory to show and introduce the actual structure and components inside the instrument to students. Students not only gain hands-on experience with technology but also have the opportunity to see some of the "inner workings" rather than simply treating the mass spectrometer as "a black box". This greatly helped students understand the construction and analysis principles of MS and motivated students to learn about scientific instruments. This comprehensive experiment can help undergraduate students to improve their overall ability and get in touch with the frontiers of analytical chemistry. This teaching practice can also provide a viable case for comprehensive chemistry experiments in other related disciplines.

Simple saccharides have a variety of biological functions, but their structural diversity and inherent structural features pose a major challenge for rapid analysis. In this work, we developed a derivative-free and ion mobility-free method for the rapid analysis of monosaccharides and disaccharides using paper spray tandem mass spectrometry. Trimeric cluster ions consisting of saccharide analytes, ligands and transition metal ions are used as precursor ions. We defined the R-value as the ratio of the intensity of the product ion that loses one molecule of ligand over the intensity of the product ion that loses one molecule of saccharide via collision induced dissociation (CID). The species and conformation of simple saccharides can be easily differentiated by calculating this R-value. With the capability of directly analyzing clinical samples using paper spray ionization, our method can be used to rapidly quantify the molar ratio of galactose to glucose in dried plasma samples to aid in the diagnosis of galactosemia. The analytical strategy provided herein has good potential to be applied to a wide range of saccharide analysis applications in the future.