Study On The Methods Of Quality Assessment And Pharmacokinetics Of Changbitong Granule

Changbitong granule,which has been included in the drug standard of ministry of public health of PRC,consists of eight herbs:Cinnamomum cassia(Guizhi), Schizonepeta tenuifolia(Jingjie),Saposhnikovia divaricata(Fangfeng),Scutellaria baicalensis(Huangqin),Angelica sinensis(Danggui),Paeonia lactiflora(Baishao), Mentha haplocalyx(Bohe),Glycyrrhiza uralensis(Gancao).It is used for the treatment of anaphylactic rhinitis,nasal obstruction,stemutation,headache and urticaria.In this dissertation,several methods for quality control have been developed to improve the drug standard of Changbitong granule,and the pharmacokinetics of cinnamic acid has been stuied in rats.Five medical materials in Changbitong granule,including Saposhnikovia divaricata (Fangfeng),Angehca sinensis(Danggui),Scutellaria baicalensis(Huangqin), Schizonepeta tenuifolia(Jingjie),Glycyrrhiza uralensis(Gancao),were identified by thin layer chromatography(TLC).High performance liquid chromatography(HPLC) methods were established to determine the contents of cinnamic acid,baicalin,baicalein, prim-O-glucosylcimifugin,4'-O-β-D-glucosyl-5-O-methylvisamminol,peoniflorin and glycyrrhizic acid in Changbitong granule.The determination could be accomplished by different mobile phase system on Diamonsil C₁₈columns.The linear ranges were 0.82～8.2μg·mL^-1(r = 0.999 9),31.0～310.0μg·mL^-1(r = 0.999 9),3.2～32.0μg·mL^-1(r= 0.999 7),2.4～24.0μg·mL^-1(r = 0.999 9),2.4～24.0μg·mL^-1(r = 0.999 9),10.8～108.0μg·mL^-1(r = 0.999 8)and 7.0～56.0μg·mL^-1(r = 0.999 7),respectively.The recoveries were 101.1%(RSD = 2.2%),100.5%(RSD = 2.0%),101.4%(RSD = 1.9%), 100.1%(RSD = 1.5%),100.7%(RSD = 1.9%),99.8%(RSD = 1.7%)and 99.4%(RSD = 1.9%),respectively.The assay methods are simple,rapid and reproducible,which provide a,quantitative basis for the quality assessment of Changbitong granule.An HPLC-UV method was developed for the determination of cinnamic acid in rat plasma.The analysis was performed on a Diamonsil^TMC₁₈(200 mm×4.6 mm,5μm) column with acetonitrile-methanol-0.5%acetic acid(39:20:60,v/v/v)as the mobile phase at the flow rate of 1.0 mL·min^-1.The UV detection wavelength was set at 280 nm. The extraction recoveries at the concentration of 0.12,0.60 and 4.80μg·L^-1were 84.9%, 82.1%and 87.0%,respectively.A linear calibration was obtained in the concentration range from 0.06 to 6.00μg.mL^-1(r = 0.998 8).Intra-day and inter-day precision(RSD) were both less than 6.0%.The method was proved to be accurate and simple,and was applied to the pharmacokinetic study of cinnamic acid in rats after i.g.administration of Changbitong granule.The main pharmacokinetic parameters were achieved as follows: C_max0.1674±0.053μg·mL^-1,T_max0.87±0.16 h,t_1/28.62±2.00 h,K_e 0.085±0.022 h^-1, AUC_0-t3.68±1.51μg·h·mL^-1,AUC_0-∞4.51±1.54μg·h·mL^-1.