| Senecio cannabifolius Less,also known as fanhuncao,belonging to the Compositae Senecio genus is a special resources in Changbai Mountain area,is currently Senecio cannabifolius Less herbs at the source of the main varieties.Senecio cannabifolius Less is the main component of prescribed preparations in Fanhuncao Granule for the treatment of pulmonary infection,chronic bronchitis,asthma,bronchitis,clinical acute respiratory infections and other diseases.The phenolic acids are the main active components of the drug effect of Fanhuncao Granule particles,and it is also an important indicator of controlling the quality of Fanhuncao.For phenolic acids research mainly concentrated in chlorogenic acid,caffeic acid,protocatechuic acid,Hyperoside,Isoquercitrin,There are many reports on pharmacodynamics,pharmacology and content determination,although some studies have reported on the pharmacokinetics of these phenolic acids,some ingredients have not yet been explored its kinetic properties.Preliminary pharmacological and pharmacodynamic study found p-hydroxybenzoic acid(PHBA),hydroxy benzene acetic acid(PHPAA)of Fanhuncao have good antibacterial and prevention and treatment of pulmonary edema activity.Understanding the pharmacokinetics of the drug in the vivo,It provides an important theoretical basis for the rational use of drugs and the formulation of drug administration program.In this paper,two active ingredient PHBA and PHPAA of Fanhuncao Granule are the research object.To establish a LC-MS/MS method for simultaneous determination of the content of PHBA,PHPAA in Fanhuncao Granule and the content of PHBA,PHPAA in the plasma samples.And the method was applied to study the pharmacokinetics of rat after administration of gastric administration.The two components in vivo pharmacokinetics were studied.Understanding the pharmacokinetics of the two components in vivo,distribution in each tissue,the contents of the study are as follows:1.Established a method for determination of the content in Fanhuncao Granule of PHBA and PHPAA,the method has strong specificity,Regression analysis of the data of PHBA and PHPAA concentration against its peak area showed a good straight line in the range of 0.005~1 μg·mL-1,R2 were 0.9998 and 0.9999 respectively.Intra-day and inter-day RSD were less than 1.91%;the RSD of Fanhuncao Granule peak area value is less than 1.96%;it show a good precision.Determination of repeatability content of PHBA and PHPAA were 0.7248 mg·g-1 and 0.1156 mg·g-1 respectively,RSD values were less than 2.0%,the method has good repeatability.The recoveries were 99.53% and 99.46% respectively.The average values of PHBA and PHPAA contents in the five batch of Fanhuncao Granule samples were 0.722 mg·g-1 and 0.1142 mg·g-1 respectively.2.To develop an LC-MS/MS method for simultaneous determinations of plasma drug concentration of PHBA and PHPAA in Fanhuncao Granule.The linear range of PHBA and PHPAA was 0.4~2000 ng·mL-1,5~2000 ng·m L-1,respectively,the intra-day and inter-day precisions(RSD)were lower than 5.00%.Accuracy levels were greater than 97.59%.The recoveries ranged from 96.67% to 98.36%,the RSD was less than 4.91%,and the matrix effect was between 89.82% and 95.94%,and RSD was less than 7.78%.The established method was proved to be rapid,high sensitivity,selectivity and suitable for the requirements of biological sample testing.3.The pharmacokinetics of rat in vivo after gastric administration was studied,and the non atrioventricular model was used to calculate the content of PHBA and PHPAA.The main pharmacokinetic parameters of PHBA and PHPAA after the administration in rats were as follows: t1/2(h)9.769±2.766,4.983±1.003;Tmax(h)1.083±0.204,0.583± 0.204;Cmax(ng·m L-1)122.9± 46.225,1273.5±316.491;AUC0-t(μg/L*h)853.95±242.035,3066.109±524.633;Cl/F(L·h-1·kg-1)0.981±0.312,0.067±0.012;MRT0-t(h)12.602±3.475,5.225±0.688.The pharmacokinetic parameters of the two components were significantly different,and PHPAA was higher than PHBA in the body,and the absorption rate was high,and the bioavailability was high.Combination of different compartmental models under fitting parameters and drug time curve,minimum AIC and F test results suggested that PHBA in rats in vivo pharmacokinetic behavior conformed to the one compartment model and weight coefficients for 1/cc,PHPAA best compartmental model for two compartment,weight coefficient 1/cc.4.The method of concentration measurement in each tissue was investigated.To study the drug distribution of heart,liver,spleen,lung,kidney,intestine,stomach and so on.Tissue samples were collected at four time points after 0.5 h,2 h,12 h and 8 h after administration.Results of drug into the body quickly distributed to various tissues,blood flow distribution of many larger organizations.The distribution of PHBA and PHPAA in each tissue was similar,but the concentration of PHPAA in each tissue was significantly higher than that in PHBA.The drug is absorbed by the small intestine and excreted by the kidney in prototype form.Two ingredients in descending order of the organizations in the concentration of the stomach,intestine,kidney,liver,lung,heart,spleen,faster elimination of the drug in the body.There was no obvious accumulation phenomenon in all tissues except gastrointestinal. |
PDF Full Text Request