Study Of 18β-glycyrrhetic Acid 3-o-glucuronide(GAM)on The Pharmacokinetics And Tissue Distribution In Rats

GAM（18β-Glycyrrhetinic acid 3-O-glucuronide）is a pentacyclic triterpenoid derivative of GA（18β-Glycyrrhizin）,and its structure is that the product of the removal of a molecule of glucuronic acid on the 3-carbon of GA.As the active intermediate of GA,GAM has enhanced pharmacological activity and mild adverse reactions.Nowadays,there are more and more researches on the synthesis and conversion of GA to GAM,and it is expected to obtain high-value GA structural derivatives.This project hopes to set up a HPLC-MS/MS way to find the plasma concentration of GAM and GCCS in rats,and to conduct research on the pharmacokinetics（PK）and tissue distribution of GAM.Accordingly it can greatly promot the discovery of new compounds on the structural modification of GA and design new pharmacological activities of GAM.1.HPLC method was used to survey and evaluate GA and GCCS in rat plasmaA specific,fast and effective HPLC-MS/MS method was established to detect GAM and GCCS,and its methodological verification was carried out.The validation in this study included the standard curve linearity,precision and accuracy,extraction recovery rate and matrix effect,stability,etc.This study was carried out to investigate the metabolic profiles and pharmacokinetics of GAM and GCCS.2.Study on the pharmacokinetics of GAM in ratsGAM doses of 7.5,15,and 30 mg/kg were designed for intragastric administration.The results showed that the AUC_0-Tand C_maxof the prototype drug GAM showed linear kinetics.The main PK parameters of GAM and its metabolite GCCS in rats were no difference between sex and gender.And compared with the 30 mg/kg dose of GA gavage,it was found that the bioavailability of GAM and GCCS was higher after gavage of GAM.3.Tissue distribution of GAM in ratsThe distribution of GAM and GCCS in rat heart,liver,spleen,lung,kidney,brain,small intestine and other tissues were investigated at 0.5,1,4,and 12 h after intragastric administration of GAM.The results showed that 0.5 h after administration,GAM can be detected in all tissues,and the distribution situation was in the order of kidney>spleen>small intestine>liver>lung>brain>heart,with the most distributed in organs such as kidney and spleen;after 12 h,the GCCS concentration reached its peak in the heart,liver,and lungs,and was hardly detectable in the brain tissue.It showed that GCCS was not liable to by means of the blood-brain barrier and had little effect on the central nervous system.The tissue distribution of GAM after intragastric administration was targeted,and it mainly accumulated in the kidney and small intestine and the generated GCCS mainly accumulated in the lungs,liver and other parts.