An integrated strategy of MS-network-based offline 2DLC-QTOF-MS/MS coupled with UHPLC-QTRAP(®)-MS/MS for the characterization and quantification of the non-polysaccharides in Sijunzi decoction

Sijunzi decoction (SJZD), a classic recipe in traditional Chinese medicine (TCM), has been applied for the clinical treatment of gastrointestinal diseases. While there are reports on pharmaceutical substances of SJZD focusing on its polysaccharides, the composition of non-polysaccharides (NPSs) has not yet been holistically clarified. In the current study, offline two-dimensional liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (2DLC-QTOF-MS/MS) was used for comprehensive NPS chemical profiling of SJZD. In addition, the MS-network of SJZD was proposed, which led to the construction of a larger in-house chemical library and accelerated qualitative processing. Four hundred forty-nine components, among which 6 were potentially novel, and 32 were confirmed by standard substances, were identified or tentatively assigned. Furthermore, based on good method validation, 19 representative components were simultaneously quantified by ultra-high-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP(®)-MS/MS). They were selected for quantification on the account of their bioactive reports on in vivo or in vitro activities, the peak intensity in the mass spectrum, and characteristic structures, which have the potential to be qualitative or quantitative markers of SJZD. The present work furthers understanding of the pharmacological effects and action mechanism of NPSs in SJZD, and provides a useful analytical approach for complex composition research of TCMs. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00216-021-03302-x.