桑叶提取物在大鼠体内的代谢产物含量测定及其药动学研究

Study on determination and pharmacokinetics of metabolites from Folium Mori extract in rats

目的:建立大鼠血浆中槲皮素、山萘酚及异鼠李素总浓度的高效液相色谱法,并计算大鼠口服桑叶提取物(Folium Moriextract,FME)后血浆中主要代谢产物-槲皮素、山萘酚及异鼠李素的药动学参数。方法:大鼠口服110 mg/kg桑叶提取物后,取其血浆并用3 mol/L盐酸水解,水解液经乙醚-丙酮混合液萃取,用HPLC法测定血浆中槲皮素、山萘酚及异鼠李素总浓度,以DAS 3.0软件计算药动学参数。结果:槲皮素、山萘酚和异鼠李素分别在0.0545~8.70,0.0954~14.7和0.0545~8.55μg/ml内呈良好线性关系,r分别为0.9979、0.9993、0.9981;三者的绝对回收率分别在85.3%~86.1%、79.4%~86.7%、62.8%~89.7%内,方法回收率均在94.7%~107%内。日内及日间精密度RSD分别小于9.5%及9.8%。以药动学软件计算的药动学统计矩参数T1/2z分别为92.7,67.9和54.2 h;Tmax分别为0.400、0.400和3.87 h;AUC(0-∞)分别为68.0、67.5和32.8 mg.h-1.L-1;MRT(0-∞)分别为128、85.2和72...

Objective:To establish a RP-HPLC method for simultaneous determination of total quercetin,kaempferol and isorhamnetin in rat plasma after oral administration of Folium Mori extract(FME).Methods:After a single dose of FME(110 mg/kg) was taken,rat plasma samples were collected.The samples were hydrolyzed with hydrochloric acid(c=3.0 mol/L),the mixed solution was extracted with etheracetone mixture.The total quercetin,kaempferol and isorhamnetin in plasma samples were determined by HPLC,pharmacokinetic parameters were calculated by DAS 3.0 software.Results:The method was linear over the concentration ranges of 0.0545-8.70,0.0954-14.7 and 0.0545-8.55 μg/ml for quercetin,kaempferol and isorhamnetin,respectively(r=0.9979,0.9993,0.9981).The absolute recoveries were 85.3%-86.1%,79.4%-86.7% and 62.8%-89.7%,respectively and the assay recoveries were all from 94.7% to 107%.The relative standard deviation(RSD) of intra-and inter-day were less than 9.5% and 9.8%,respectively.The main pharmacokinetic parameters were as follows:T1/2z was 92.7,67.9 and 54.2 h;Tmax was 0.400,0.400 and 3.87 h;AUC(0-∞) was 68.0,67.5 and 32.8 mg/h/L;MRT(0-∞) was 128,85.2 and 72.0 h for quercetin,kaempferol and isorhamnetin,respectively.Conclusions:The method established in this study is accurate,reliable and reproducible,and can be applied for determination of total quercetin,kaempferol and isorhamnetin in rat plasma after oral administration of FME;the pharmacokinetic studies showed that the distribution of drugs is rapid and elimination is very slow.