Tissue Distribution and Biliary Excretion of a Classical Traditional Chinese Medicine Shengjiang Xiexin Decoction in Rats Analyzed by Ultra‐High Performance Liquid Chromatography Coupled to Mass Spectrometry

ABSTRACT The side effects caused by chemotherapeutic agent irinotecan (CPT‐11), such as diarrhea and steatosis, limit its clinical application. Shengjiang Xiexin decoction (SXD), a classical traditional Chinese medicine, is utilized to mitigate CPT‐11‐induced diarrhea. In our previous study, SXD was found to influence the hepato‐intestinal metabolism of CPT‐11. To better understand the potential active constituents, it is essential to explore the hepato‐intestinal distribution and excretion characteristics of SXD. In this study, an ultra‐high‐performance liquid chromatography coupled to quadrupole/orbitrap high‐resolution mass spectrometry (UHPLC‐Q‐Orbitrap HRMS) was used to qualitatively characterize prototypes and metabolites of SXD in the liver, intestine, bile, and feces. The results demonstrated that following SXD administration, extensive biotransformation occurred through the liver–gut axis system. SXD underwent hepatic and intestinal metabolism, followed by elimination through bile and feces. A total of 283 SXD‐related xenobiotics were found in vivo, including 174 prototypes and 109 metabolites. Among these, 146 constituents were present in both the liver and intestines. Flavonoids were the major constituents of SXD distributed in rat tissue. The metabolic pathway primarily involves glucuronidation, sulfation, demethylation and glycosylation, decarboxylation, ring cleavage, and hydrogenation. Furthermore, a UHPLC‐tandem mass spectrometry (UHPLC‐MS/MS) method was developed to evaluate the biliary excretion of 19 prototypes from SXD. The cumulative biliary excretions of flavonoid‐glycosides (baicalin, wogonoside, and oroxylin A 7‐ O ‐glucuronide) and triterpene‐glycosides (glycyrrhizic acid) were greater than those of their corresponding aglycones. Nevertheless, the cumulative biliary excretions of chalcone glycosides (isoliquiritin) were decreased compared with those of their aglycones. The amounts of alkaloids (magnoflorine, berberine, coptisine, jatrorrhizine, palmatine, and epiberberin) in bile over 8 h ranged from 506.31 to 8073.92 ng/g. These findings enhance our understanding of SXD's metabolic fate and offer important insights into the synergistic action mechanisms of its absorbed constituents.