Investigate On Pharmacokinetics Of Traditional Chinese Medicine Salvia Mihiorrihiza And Pollen Typhae

Study on drug metabolism plays an important role in drug research and development. Thus, metabolite analysis for chemical constituents of traditional Chinese medicine attracts much more attention. In this thesis, pharmacokinetics of salvia mihiorrihiza and Pollen Typhae were determined by CE and HPLC method, the obtained results were concluded as in the following:1. A micelle eletrokinetic capillary chromatography (MEKC) method was established to determine Danshensu in rabbit blood plasma. The plasma was deproteinized using perchloric acid, extracted by ethyl acetate, and followed by analysis under the optimization conditions. The linear range for Danshensu was 0.4-400μg/mL, and the LOD was 0.08μg/mL. The precisions expressed as the relative standard deviation (RSD) were 1.1-5.8%, average recoveries were 84.95-104.20%. These results showed that the validated method have wide linear range, good sensitibity and accuracy, has been successfully applied in the pharmacokinetic study of Danshensu.2. The validated MEKC method has been successfully applied for the pharmacokinetic study of Danshensu after intragastric administration of the aqueous extract from salvia mihiorrihiza. The concentration-time curve and the data of pharmacokinetic parameters indicated that the concentration-time changes of Danshensu in rabbits were adequately fitted to two-compartment open mode. T_max of Danshensu was 46.9 min, T_1/2a was 46.9 min and T_1/2β was 69.3min.3. A reversed-phase HPLC method was developed for simultaneous determination of three flavonoids, quercetin (QU), kaempferol (KA) and isorhamnetin (IS), in rabbit blood plasma samples. The plasma was deproteinized using trichloroacetic acid and extracted by n-butanol-acetoacetate mixture. The analyte was separated on a C₁₈ column (4.6 mm×150 mm, 5μm) with acetonitrile and 0.1% phosphonic acid in water (27:73, V/V) as mobile phase. The concentrations of QU, KA and IS for the developed method were linearly related to their responses in the range of 0.05 to 2.5μg/mL, the LOD was 0.03, 0.02 and 0.02μg/mL, respectively, and precision and accuracy were within±15%, indicating that the validated method have good sensitibity and accuracy, and could been applied for the pharmacokinetic study of QU, KA and IS.4. The concentration of QU, KA and IS were simultaneous determined by HPLC method after a single oral dose hydrolysate of Pollen Typhae was administered to rabbits. The pharmacokinetic parameters were calculated by software Drug And Statistics (DAS). The results showed that the concentration-time curves of three flavonoids in rabbits were adequately fitted to two-compartment open mode, T_max of QU, KA and IS were 32.5, 35.0 and 35.0 min, respectively, t_1/2a were 41.67, 16.16 and 29.73 min, respectively, and V1/F werel4.18, 9.48 and 84.01 L/kg, respectively.5.β-cyclodextrin are capable of forming inclusion complexes with QU, KA and IS to improve their solubility, bioavailability. The inclusion constants and thermodynamic parameters in the process of interactions of three flavonoids withβ-cyclodextrin were investigated using mobility shift method by capillary electrophoresis, and their inclusion mechanism was explained.