Comparative pharmacokinetics of Ding‐Zhi‐Xiao‐Wan preparation and its single herbs in rats by using a putative multiple‐reaction monitoring UPLC‐MS/MS method

Abstract

Introduction The formula of Chinese medicine, Ding‐Zhi‐Xiao‐Wan (DZXW), has the distinct feature of compatibility therapy, which is attributed to the interactions of multi‐herbs. However, the quantification problem caused by the absence of pure reference standards is a bottleneck to clarify the compatibility advantages from the perspective of pharmacokinetics (PKs). Objective This study aimed to develop a putative multiple‐reaction monitor (PMRM) strategy for exploring the comparative PKs of DZXW and its single herbs. Methods First, precursor ion and tandem mass spectrometry (MS/MS) chromatograms were obtained via ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight MS (UHPLC–Q‐TOF‐MS) under different collision energy (CE) values. Then, the two most abundance ions in the MS/MS chromatograms were chosen as product ions, and CE values were selected according to the abundance of the product ion peaks. Next, a PMRM strategy consisting of optimal MRM parameters was constructed. Finally, the established PMRM parameters were imported to UHPLC coupled with triple quadrupole MS (UHPLC–TQ‐MS) for quantification. Results The strategy was exemplified by the comparative PK study of DZXW and its single herbs. This strategy could extend the PK scopes of multi‐components. The quantitative results displayed substantial variations in PK parameters between DZXW and its single herbs. Conclusion The PK parameters indicated that the DZXW formula could increase the exposure levels of most ingredients and reduce the maximum concentration (Cmax) of Radix Polygala, indicating that herb compatibility could produce synergistic effects and diminish possible toxic effects. This study provides a viable orientation for the compatibility investigation of traditional Chinese medicine.

A Comparative Study of Serum Pharmacochemistry of Kai-Xin-San in Normal and AD Rats Using UPLC-LTQ-Orbitrap-MS

“…The residue was extracted with 6-fold 70% ethanol under reflux for 1 h, followed by filtration while hot. The above filtrates were combined and concentrated at 65 °C until there was no ethanol dripping from the condenser [ 32 ]. The ethanol extract was freeze-dried, and 89.6 g of dry powder was obtained with a yield of 22.4%.…”

Poria cocos could ameliorate cognitive dysfunction in APP/PS1 mice by restoring imbalance of Aβ production and clearance and gut microbiota dysbiosis

“…Our laboratory has investigated the chemical characterization, metabolic pathways, and pharmacokinetic (PK) process of PC (Feng et al, 2019; Y. Sun et al, 2020). Most of the active ingredients were found to be distributed in the feces and blood, with one active ingredient in the brain.…”

“…In addition, it is widely used as a constituent of many formulae (including ding-zhi-xiao-wan, dang-guishao-yao-san, xiao-yao-wan), wherein PC plays a major constituent for the treatment of neurodegenerative diseases (Liu, Zheng, Du, Li, & Qin, 2019;Luo, Wang, & Zhang, 2016). Our laboratory has investigated the chemical characterization, metabolic pathways, and pharmacokinetic (PK) process of PC (Feng et al, 2019;Y. Sun et al, 2020).…”