Analysis Of The Plasma Pharmacokinetics Of Quick Heartache Side Of Xiaoxuming Soup Ingredients

The prescriptions of Traditional Chinese medicine (TCM) were usually combination drugs, composed of several medicinal herbs and the compatibility of the medicinal herbs in prescriptions directly affects the therapeutic and toxic effects of TCM. It was proposed that the different compatibility of TCM might change the in vivo process of active or toxic compounds and finally affect therapeutic and toxic effects of TCM prescriptions.This paper contained two parts, studied on combination principle from the pharmacokinetics angle and quantitation determination of a combination drug in each part.In the first part, the combination principle was investigated by studying the pharmacokinetic characters of Su-Xiao-Xin-Tong (SXXT). SXXT prescriptions was a new Chinese prescription, has the efficacy of removing heat to cool blood, promoting blood circulation to arrest pain, it was commonly used for treating angina pectoris and coronary heart disease. Paeonol was the main active constituent in Cortex Moutan and SXXT. It was used as the marker compound for quality control of SXXT.In the present work a sensitive and specific liquid chromatography connected with electrospray ionization mass Spectrometry (LC-ESI-MS) method has been developed and validated for the identification and quantification of paeonol in rat plasma was developed, to study the pharmacokinetics and to investigate the in vivo interaction of the three constituent parts in SXXT and influence of the pharmacokinetic process of the main active constituent (paeonol). Compatibility principles of SXXT were explored at the angle of pharmacokinetics in vivo.Paeonol and internal standard (IS) were isolated from plasma samples by liquid-liquid extraction with chloroform. The chromatographic separation was accomplished on a Zorbax-SB C₁₈ column (100×2.1 mm, 3.5μm). The mobile phase consisted of acetonitrile and 0.1% aqueous formic acid (64 : 36) was delivered at a flow rate of 0.2 mL/min. Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The method was proved to be sensitive and specific by testing six different plasma batches. Linearity was established for the range of concentrations 0.0525-15.75μg/mL with a coefficient of determination (r) of 0.9995 and good accuracy and precision. The RSD of intra-and inter-day precision was lower than 9.3% and accuracy ranged from 93.7 to 102.3%. The lower limit of quantification was 0.0525μg/mL. The established method was fit-for-purpose to determine the concentration of paeonol for pharmacokineticstudies. The pharmacokinetics of different compatibility prescriptions ofSu-Xiao-Xin-Tong was studied and compared. The results were as following:1. From the concentration-time curve, it can be observed that the absorption of paeonolwas rapid, with peak concentrations occurring less than 20 min for each groups after oraladministration.2. As calculated from the mean plasma concentrations of paeonol following oral administration of the three different prescriptions. After administration of compatibility prescription, T_max were much earlier than administration of Danpi extract alone, AUC_0-t, AUC_0-8 and AUMC_0-8 were also increased after administration of compatibility prescriptions. These result showed that the absorption and the bioavailability of paeonol was improved by compatibility prescription.3. Cl was decreased and MRT_0-8 was increased after administration of compatibility prescriptions. These results indicated that elimination of paeonol was slow down from rats' body and paeonol could take effects longer time in rats.The results provide scientific data for the further study of compatibility prescription and useful references for the modern pharmacokinetic study of Traditional Chinese Medicine.In the second part of the paper, a rapid RRLC method was developed and validated to determine the eleven main constituents in a TCM prescription named "Xiao-Xu-Ming-Tang" simultaneously. The method was precise and accurate. Each constituent showed a good linearity with coefficient (r) less than 0.999. The intra-and inter-day precision (RSD.%) were lower than 3.5% and 4.6% respectively.From the results, it can be seen that the contents of the constituents in the active fraction were greater than in the extract of Xiao-Xu-Ming-Tang. These proved that the process of making the active fraction of Xiao-Xu-Ming-Tang had enriched the contents of active compounds.