Analysis Of The Absorbed Components Of Shuangdan Decoction And A Study On The Phramacokinetics Of Four Active Compounds

High-performance liquid chromatography/mass spectrometry (HPLC/MS) has become a technique which has been used routinely in a wide variety of application areas since 1990s. Based on the high sensitivity and high selectivity characteristics of HPLC/MS, it has been an extremely effective tool in pharmaceutical sciences, especially in the area of biopharmaceutical analysis.Identifying active components of traditional Chinese medicines (TCMs) responsible for the pharmacological effects is the key part in the research to achieve modernization of TCMs. In this dissertation, HPLC/ESI-MS based methods were proposed in the studies of serum pharmacochemistry and pharmacokinetics of Shuangdan decoction, which is a clinical used botanical drug for the treatment of cardiovascular disease.High-performance liquid chromatography/tandem mass spectrometric method was employed in the analysis of rat plasma samples after oral administration of Shuangdan granules. The structure of 16 components from Shuangdan granule were identified or tentatively elucidated. They were gallic acid, danshensu, caffeic acid, protocatechuic aldehyde, paeoniflorin, salvianolic acid D, salvianolic acid G, rosmarimic acid, lithospemic acid, salvianolic acid B, salvianolic acid C, paeonol, neocryptotanshinone, dihydrotanshinone I, tanshinone V, cryptotanshinone, respectively. Furthermore, five metabolites were tentatively designated to be 2-hydroxyacetophenone-4-O-glucuronide, 4-methoxyacetophenone-2-O-glucuronide, 2,4-dihydroxy-acetophenone-5-O-sulfate, 2-hydroxy-4-methoxyacetophenone-5-O-sulfate, resacetophenone, respectively. They were confirmed to be metabolites of paeonol.According to the results of qualitative analysis, variations of the concentration of some identified components in vivo were investigated, employing high-performance liquid chromatography/single-quadrupole mass spectrometric method. Preliminary kinetic study of 10 absorbed components in rabbit plasma during 24 hours after administration was carried out.Finally, a sensitive high-performance liquid chromatography/mass spectrometric method was developed for the simultaneous determination of danshensu, protocatechuic aldehyde, paeoniflorin and paeonol in rat plasma. The results indicated that the method was simple, accurate and specific. The intra-day and inter-day precision was less than 5.2% and 9.9%, respectively. This method was successfully applied to the pharmacokinetic study on these 4 active compounds of Shuangdan decoction. Non-compartmental pharmacokinetic parameters were calculated using computer program "Topfit".