Systematically characterization of in vivo substances of Ziziphi Spinosae Semen in rats by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis.

Ziziphi Spinosae Semen (ZSS), the seeds of Ziziphus jujuba var. spinosa, is widely used in China or other Asian countries for the treatment of insomnia and palpitation. In our previous work, chemical constituents in ZSS were profiled by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF MS). Notably, characterization of substances in vivo was of great importance to reveal the therapy basis or mechanism in further work. Till now, there were few reports about in vivo substances' investigation of ZSS. In the present study, an integrated strategy contained represented compounds and diagnostic ions extraction was applied to characterize metabolism feature of ZSS in rats based on UHPLC/Q-TOF MS method. First, the metabolic information of four compounds (spinosin, isovitexin, jujuboside B, betulinic acid) featuring three representative chemical structures (flavonoids, saponins, terpenes) in ZSS was conducted, and their metabolism features were summarized, especially for flavonoid C-glycosides. Second, the absorbed compounds and representative compounds-related metabolites were quickly screened out; during this time, the diagnostic ions were sorted out. Last, with the help of diagnostic ions and summarized metabolic reactions, other metabolites were characterized. As a result, a total of 151 xenobiotics (58 prototypes and 93 metabolites) were identified or tentatively characterized in rats after ingestion of ZSS. Among them, 16 substances were presented in plasma, 114 in urine, 51 in bile, and 120 in feces, respectively. Hydrogenation, hydrolysis, and glucuronidation were the major metabolic reactions of ZSS in rats. The present study provided meaningful data for further pharmacological mechanism research or pharmacokinetics evaluation of ZSS.

Metabolic profiles and pharmacokinetics of Qingre Xiaoyanning capsule, a traditional Chinese medicine prescription of Sarcandrae Herba, in rats by UHPLC coupled with quadrupole time-of-flight tandem mass spectrometry.

Qingre Xiaoyanning capsule is a famous traditional Chinese medicine prescription which consisted of Sarcandrae Herba (also named Caoshanhu in China) water extract for the frequent treatment of inflammation and immunity related diseases. Until now, the in vivo bioactive components of Qingre Xiaoyanning capsule have not yet been fully addressed. In this study, a total of 42 xenobiotics including 20 prototypes and 22 metabolites were identified in rats after oral administration of Qingre Xiaoyanning capsule using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Subsequently, isofraxidin and rosmarinic acid, two bioactive components with high exposure in rat plasma, were quantitatively analyzed, while another 20 major absorbed components were semi-quantitatively measured, to investigate together the pharmacokinetics behavior of Qingre Xiaoyanning capsule. Taken together, this study provided comprehensive knowledge of in vivo disposal of this prescription, which could help reveal the potential bioactive components, and would be conducive to further pharmacological mechanism research as well as quality control approach improvement of Qingre Xiaoyanning capsule and Sarcandrae Herba related prescriptions.