Pharmacokinetic Study Of Piceatannol-3'-O-?-D-Glucopyranoside In Rats

Piceatannol-3'-O-?-D-glucopyranoside?PG?,a typical stilbene glycosides,is supposed to be one of the major active compounds isolated from the root and rhizome of Rheum lhasaense A.J.Li et P.K.Hsiao,the chemical name is 3,5,3',4'-trihydroxy-stilbene-3'-O-?-glucoside.According to literatures,PG plays an important role in a wide spectrum of pharmacological properties including anti-inflammation,anti-arteriosclerosis and lung protective effect.In the present study,a HPLC-UV method was established for the analysis of the contents and related compounds of PG and a HPLC-HRMS method was developed and validated for the quantification of piceatannol-3'-O-?-D-glucopyranoside in rat plasma and was applied to a pharmacokinetic study,this will provide theoretical basis for further research.The extraction and purification technology of PG from Rheum lhasaense A.J.Li et P.K.Hsiao was investigated.The preliminary purification of PG was used D101 macroporous resin,and then crude extract was further purified on reverse C₁₈8 open column.Then,A HPLC-UV method was established for the determination of the content of PG.The separation was performed on Agilent Zorbax SB-C₁₈ column?150×4.6 mm,5?m?.Results indicated that PG showed a good linear relationship?r=0.9999?over the concentration range of 2²0?g·mL^-1.The accuracy was within the range of 100 to 103%,and the precision was 1.12%.And the contents of PG of three batches?180420,180506,180515?were 100.51%,100.21%and99.68%,respectively.Another HPLC-UV method was established for the analysis of the related compounds of PG,and the stability of PG under stressed conditions were also investigated,including strong acid,alkali,oxidant,light and high temperature.The results showed that PG was not stable under strong alkali condition,and the degradation rate was accelated by high ion strength.It was unstable to light and the degradation rate increased with the increase of illumination intensity,and showed a linear correlation with time.PG showed good stability under the conditions of oxidation,acidity and heat.Finally,three related substances were detected and the corresponding contents of them were 0.11%,0.13%,0.02%,the total content of related substances was 0.27%.A HPLC-HRMS method was developed and validated for the quantification of PG in rats'plasma after a single intravenous injection at three different dosages(1.25,3.75 and11.25 mg·kg^-1).The calibration curve was linear over the concentration range of 5⁵00ng·mL^-1?r=0.9984?with a lower limit of quantitation?LLOQ?of 5 ng·mL^-1.The intra-day and inter-day precision were less than 6.71%for the analyte and accuracy was from-2.00 to6.74%.The recovery and matrix effect of the analyte were all satisfactory.The accuracy for dilution at 30 or 900 folders was within±15%and precision<15%.After an intravenous injection of PG,the main pharmacokinetic parameters obtained by noncompartment model were as follows:AUC_0-?were 6370.56±1899.74,1948.94±598.20and 577.24±83.50 ng·h·mL^-1;Vss were 0.39±0.15,0.37±0.09 and 0.44±0.11 L·kg^-1.The results showed that PG was widely distributed and rapidly eliminated.