Study On Pharmacokinetics And Biodistribution Of Active Ingredients In Chinese Herbal Medicines Polygonum Chinense Linn And Hedyotis Diffusa Willd In SD Rats By UHPLC-MS/MS

UHPLC-MS/MS is one of the most commonly used methods for the determination of trace ingredients which has the characteristics of high accuracy,sensitivity,rapid separation,and analysis.This technology has significant advantages in the study of pharmacokinetics and tissue distribution of pharmaceutical ingredients in vivo,providing a reliable,simple and rapid analytical method.In this paper,UHPLC-MS/MS method was used to simultaneously determine the blood concentration of various effective components from TCM in SD rats to investigate the pharmacokinetics and tissue distribution.A sensitive,simple,rapid,efficient and reliable UHPLC-MS/MS method has been developed and validated for simultaneous quantitative determination of bioactive ingredients(protocatechuic acid,gallic acid,neochlorogenic acid,caffeic acid,syringic acid,epicatechin,p-coumaric acid,scopoletin,ferulic acid,scutellarin,isoquercitrin,hyperoside,avicularin,quercitrin,and luteolin)in rats plasma and tissues(including heart,liver,spleen,lung,kidney)after oral administration of Polygonum chinense Linn extract,using danshensu(IS1)and rutin(IS2)as internal standards for the corresponding analytes and to study their pharmacokinetics and biodistribution.Fifteen boiactive ingredients and two internal standards achieved baseline separation within 19 minutes.The verification method exhibited an excellent excellent linearity in a wide concentration range R2>0.9963.The intra-day and inter-day precisions(RSD)were less than 9.12%and the accuracies(RE)ranged from-4.02%to 6.32%,respectively.The mean extraction recoveries and matrix effects of analytes and ISs from rat plasma and various tissues ranged from 83.65%to 101.2%and 86.20%to 110.2%,respectively;the stability of the analyte is good.All these data indicated that the method was reliable and accurate.The validation method of this study was used to assess the reliability of the data through the U.S.Food and Drug Administration guidelines for bioanalysis and provides useful value for the pharmacology,toxicology and clinical medication safety of Polygonum chinense Linn.Analytical method based on UHPLC-MS/MS technology for simultaneous determination of fourteen bioactive compounds(including gallic acid,protocatechuic acid,geniposidic acid,caffeic acid,scopoletin,ferulic acid,apigenin-7-o-glucuronide,daidzein,apigenin,ursolic acid,oleanolic acid,β-sitosterol,coniferin,and stigmasterol)in rat plasma and tissue after oral administration of Hedyotis diffusa Willd extract was established and danshensu and icariin were used as internal standards(IS1 and IS2).The present analytical method exhibited excellent linearity(R2≥0.9985)and the lower limits of quantification were 1.0-80 ng/mL for all the analytes.The intra-and inter-day precisions(RSD%)were less than 10.3%,while the accuracy was ranged from-7.34%to 9.10%.Extraction recovery ranged from 85.02 to 112.0%and the matrix effects ranged from 85.12%to 109.6%,respectively.All analytes exhibited good stability under four different environmental conditions.The analytical method of this study has been successfully applied to the pharmacokinetic study and tissues distribution of fourteen components of Hedyotis diffusa Willd extract in rats,and make a contribution to provide reliable information of quality control,pharmacological research and medication safety for this herb.