Study On The Pharmacokinetic Fingerprint Of Salviae Miltiorrhizae Radix Et Rhizoma Using Biopartitioning Microemulsion Liquid Chromatography

PurposeSalviae miltiorrhizae Radix et Rhizoma (Danshen) was chosen as the model herbin this study. Using the biopartitioning microemulsion liquid chromatography andquantitative retention-activity relationships, the relationship concerning thepharmacokinetic data of multicomponent in Chinese traditional medicine andretention data of chromatography was established. And thus the pharmacokineticfingerprint concerning the activity of components in Danshen was mapped.Methods and Results1Study on the retention of major components of Danshen in microemulsion liquidchromatography systemThe separation of components in Chinese traditional medicine is the foundationof the high throughput screening platform of active constituents and the mapping ofbiologic fingerprint. The retention of nine hydrophilic and hydrophobic componentsof Danshen in different microemulsion system was investigated in this part. Thesingle factor experiment was adopted to investigate the retention of components ofDanshen in mcroemulsions consisting of different surfactants, oil phase and additives. In addition, different lot of column and pH of aqueous phase were investigated aswell.2Pharmacokinetic studies of DSA in ratThe water extraction method was used for the extraction of DSA. The aqueousextract solution was purified using macroporous resin and concentrated intowater-soluble extract. The HPLC method was developed for the simultaneousdetermination of SA1, SA4and SA5in water-soluble extract. Further, the HPLCmethod was developed for the determination of DSA in plasma of rat. TheSpragueDawley rats were chosen as experimental subjects. The blood samples werecollected from orbital vein of rats after receiving a single oral dose of thewater-soluble extract by intragastric administration. The3p97software package wasused to calculate the parameters of pharmacokinetics.3Pharmacokinetic studies of TS in ratThe ethyl acetate reflux extraction method was used for the extraction of TS andthe HPLC method was developed for the determination of TS2and TS3in lipophilicextract. Further, the HPLC method was developed for the determination oftanshinones in plasma of rat. The SpragueDawley rats were chosen as experimentalsubjects. The blood samples were collected from orbital vein of rats after receiving asingle oral dose of the lipophilic extract by intragastric administration. The3p97software package was used to calculate the parameters of pharmacokinetics.4Establishing quantitative retention-activity relationships (QRAR) and mapping thepharmacokinetic fingerprint of Danshen35components in Chinese traditional medicine were chosen as the model drugs.The microemulsion liquid chromatography systems were investigated concerning thepredictive ability of pharmacokinetic parameters. The optimal system was used toestablish the QRAR via the regression of support vector machine (SVM). Furthermore,the test set including the major hydrophilic and lipophilic components in dansen wasemployed to validate the predictive ability of the model. The model displayed goodpredictive ability and rubustness. Finally, the pharmacokinetic fingerprint of Danshen was mapped using the QRAR model.