The Study On Tissue Distribution And Excretion Of GDH In Rats

Flavonoids exist generally in nature which are highly bioactive. Flavonoid is an effective hypolipidemic traditional Chinese medicine by improving blood circulation and decreasing cholesterol. Therefore, 3-OH was replaced by CH3O- 、 CH3COO- 、CH3CH2COO- to modify structure taking 2- phenyl chromone as the mother nucleus. Those compounds were active in vitro, while not active in vivo. Fortunately, we found an actcive metabolite whose structure was possessed 3-OGlu instead of 3-OH, named GDH(3’,4’-dimethoxy-flavonol-3-o-glucoside). According to provisions for new drugs approval, pre clinical drug research includes pharmacology, toxicology, animal pharmacokinetic, etc. Second Military Medicine University synthesized GDH and studied the reaearch of absorption. The aim of study is to explore the regularity of in vivo tissue distribution of GDH in SD rats and research GDH in urine, feces and bile excretion in SD rats, which can improve the pharmacokinetic research of GDH in animals in vivo.1. Tissue distribution study on GDH in SD ratsObjecive: To establish an LC-MS/MS method for determination GDH in SD rats tissue, and to evaluate the distribution rule of GDH in SD rats.Methods: We collected the tissue samples at different times after 42 rats were orally administration of a single dose(30mg/Kg) of GDH. The concentration of GDH in tissue were determined after samples were homogenated, hydrolyzed and liquid-liquid extracted.Results: GDH were distributed in most of all tissues collected, such as small intestine, heart, spleen, liver, spleen, lung, stomach, kidney, brain, skeletal musle, fat, ovary, uterus and testis, especially in spleen, lung, kidney, small intestine, liver and heart, GDH achieved rapidly the peak concentration, which were higher than in others, and that in genital were higher than that in musle and adipose tissue.Conclusions: GDH has a prompt and extensive tissue distribution in SD rats.2 Excretion study on GDH in SD ratsObjecive: To determinate GDH in urine, feces and bile by using LC-MS/MS, and to explore the rule of excretion as well as the main pathways of excretion.Methods: After six rats were orally administration of GDH at a single dose(30mg/Kg), we collected the samples from urine and feces at different times. At the same time, after another six rats were orally administration of GDH at a single dose(30mg/Kg), we collected the samples from bile at different times.The concentration of of GDH in urine, feces and bile were measured by LC-MS/MS. Thus, we calculated the rate of urinary, fecal and biliary excretion of GDH, respectively.Results: The accumulation excertion rate in urine and feces were(0.3034±0.0671)% and( 0.7104±0.1287) %, respectively, during 72 h after administration while(0.7762±0.1593)% in bile during 24 h after oral administration. Obviously, the total excretion rate of GDH by the main three courses, excretion was only 1.79%.Conclusions: The prototype of GDH in urinal, fecal and biliary excretion was few, which shows that GDH has a extensive metabolic process in SD rats.