Study On Preparation Quality Control, Human Metabolite Of Andrographolide And Stability In Vitro Of Cichoric Acid

This article mainly established methods for determination the twobioactive components in the preparations of Andrographis paniculata(Burm. F.) Nees; andrographolide and metabolites in human plasma andcichoric acid extracted from Echinacea in digest liquids and humanplasma by high performance liquid chromatography coupled withelectrospray ionization mass spectrometry (HPLC-ESI-MS) or ultraviolet(HPLC-UV). The established methods can be used to control the qualityof the preparations containing andrographolide (AP) and dehydro-andrographolide (DAP); supply reliable data for pharmacokinetics studyof AP and investigate the stability of cichoric acid in vitro. This workplays an important role in offering reference data for the design of thedosage forms, the preparation of pure cichoric acid, the security ofadministration.This study has mainly finished the following work:1. An analytical method was developed for the simultaneousdetermination of AP and DAP in the capsule preparation byHPLC-ESI-MS. This method has the advantage of short analytical time,simple sample preparation and specificity to control the quality of thepreparations. It provides the reference for the amending of quality controlcriterion of the preparation. 2. In this paper, a rapid method based on HPLC/ESI-MS for thequantitative determination of AP and corresponding metabolite in humanplasma after oral administration of 50 mg of AP capsule to volunteers hasbeen developed and validated. A liquid-liquid extraction (LLE) procedurewas selected to isolate AP. We hydrolyzed plasma samples by acidichydrolysis in microwave. The AP conjugated with glucuronic acid andsulfate groups was determined by gradient elution. The limit ofquantification of the method was 9.9 ng/mL. That was successfullyapplied to the phannacokinetics study.3. The stability of cichoric acid in simulated gastrointestinal fluidand human plasma was investigated by HPLC-UV in order to make clearthe factors affecting drug absorption. The effects of various pH values onthe stability of cichoric acid were also examined. Cichoric acid has goodstability under the condition of pH 3-5 in the accelerated degradationexperiment. The cause of degradation of cichoric acid was investigatedby HPLC/ESI-MS.