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

Abstract

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). 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 ether acetone mixture. The total quercetin, kaempferol and isorhamnetin in plasma samples were determined by HPLC, pharmacokinetic parameters were calculated by DAS 3.0 software. 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: T(1/2z) 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. 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.