Pharmacokinetics of Nine Effective Ingredients of Chaihuyujinxiang Granules in Rats with Depression by UPLC-MS/MS

Pharmacokinetics reflects the laws of medicine absorption, distribution, metabolism and excretion in the body. The multi-component pharmacokinetic study of traditional Chinese medicine (TCM) is a bridge between the chemical composition and pharmacodynamic activity, and it is the key to reveal the pharmacodynamic material basis of TCM and guide the rational use of clinical medicine. Therefore, it is very necessary to elucidate the pharmacokinetic characteristics of the main pharmacodynamic components of medicines in disease models. At present, the method of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has unique advantages in the analysis of complex TCM components and their metabolites in vivo, which is a powerful method for pharmacokinetic analysis. Chaihuyujinxiang Granules (CHYJX) is an evolution of the classic prescription Chaihu Shugan San, which is composed by Radix Bupleuri, Glycyrrhiza uralensis Fisch, Cyperus rotundus L, Radix Curcumae Aromaticae extracts and Ostrea gigas thunberg superfine powder. In this study, a method of UPLC-MS/MS was established for simultaneous quantification of saikosaponin a, saikosaponin c, saikosaponin d, glycyrrhetinic acid, liquiritin, isoliquiritigenin, liquiritigenin, formononetin, glycyrrhizic acid in rat plasma. The methodological investigation including selectivity, residue, linearity, precision and accuracy, extraction recovery rate and matrix effect, stability all met the requirements of quantitative analysis for biological samples. The rat model of depression was constructed by the method of chronic unpredictable mild stress (CUMS). The 24 h dynamic changes of the nine main pharmacodynamic components in the plasma of depressed rats after intragastric administration of CHYJX were studied. The contents of 9 components in rats showed regular changes over time. Peak time (Tmax), half-life (t1/2), area under the cure AUC(0-t), MRT(0-t) were calculated as 0.27-4.06 h, 3.51-7.76 h, 70.06-1 280.4 μg·h/L, 7.13-11.48 h, respectively. The CHYJX could be rapidly absorbed in the gastrointestinal tract, and the elimination speed was fast in the body, which showed that the medicine was not easy to produce residue and accumulation, and had satisfied safety requirements. According to the medicine-time curve results, it was found that saikosaponin a, saikosaponin c, saikosaponin d, isoliquiritigenin, liquiritigenin, and glycyrrhizic acid all had a second absorption peak, which indicated that the 6 components might undergo enterohepatic circulation, transformation of different compounds, multi-site absorption or intestinal efflux in vivo. The study not only provides a reference method for the simultaneous quantification of the 9 components in plasma, but also provides theoretical support for the basic research on pharmacodynamic substances and clinical application of CHYJX.