A sensitive LC-MS/MS method-based pharmacokinetic study of fifteen active ingredients of Yindan Xinnaotong soft capsule in rats and its potential mechanism in the treatment of cardiovascular diseases

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1220; p. 123663
• Main Authors: Li, Jun-Ming, Huang, An-Xian, Yang, Liu, Li, Ping, Gao, Wen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2023
• Subjects: Animals; Capsules; Cardiovascular Diseases - drug therapy; Chromatography, High Pressure Liquid - methods; Chromatography, Liquid; Drugs, Chinese Herbal - chemistry; LC-QQQ MS; Molecular docking; Molecular Docking Simulation; Network pharmacology; Pharmacokinetics; Rats; Tandem Mass Spectrometry - methods; LC-QQQ MS; LLOQ; UHPLC-QQQ MS; C-T-D; PPI; MRM; I/R; Molecular docking; MRT; AUC; QC; t1/2; V; Network pharmacology; ESI; Cmax; GC–MS; RSD; QTOF MS; CL; IS; MAPK; CVD; LC-MS; RE; YDXNT; Tmax; Pharmacokinetics; TCM
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2023.123663

•A sensitive and accurate UHPLC-QQQ MS method was developed and validated for the quantification of 15 components of YDXNT in rat plasma sample.•The developed method was successfully applied to the pharmacokinetic study of YDXNT in rats after oral administration.•MAPK signaling pathway was a crucial pathway for YDXNT in the treatment of cardiovascular diseases. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese herbal preparation for the clinical treatment of coronary disease. However, there is a lack of pharmacokinetic studies on YDXNT, and its active ingredients and their mechanism in the treatment of cardiovascular diseases (CVD) are still unclear. In this study, 15 absorbed ingredients in rat plasma after oral administration of YDXNT were quickly identified based on liquid chromatography tandem quadrupole time-of-flight mass spectrometry (LC-QTOF MS), and then a sensitive and accurate quantitative method based on ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-QQQ MS) was established and validated for simultaneous determination of the 15 ingredients of YDXNT in rat plasma, which was then applied to the pharmacokinetic study. Different types of compounds showed various pharmacokinetic characteristics, for instance, ginkgolides with higher maximum plasma concentration (Cmax), flavonoids presenting concentration–time curve with double peaks, phenolic acids with shorter time to reach maximum plasma concentration (Tmax), saponins with long elimination half-life (t1/2) and tanshinones showing fluctuant plasma concentration. Then the measured analytes were regarded as effective compounds and their potential targets and mechanism of action were predicted by constructing and analyzing the compound-target network of YDXNT and CVD. Those potential active compounds of YDXNT interacted with targets such as MAPK1 and MAPK8, and molecular docking showed that the binding free energies of 12 ingredients with MAPK1 were less than −5.0 kcal/mol, indicating that YDXNT intervened in the MAPK signaling pathway to display its therapeutic effect on CVD.