Studies On The Quality Control Method Of Natural Substances In Compound Bismuth Aluminate Tablet

Recently,traditional Chinese medicines(TCM)/herbal medicines(HM)has attracted more and more attention around the world because of its distinguished therapeutic effects with minimal or negligible side effects.Meanwhile,TCM/HM quality control has raised considerable concern for their safety and efficacy in clinical applications.TCM/HM composition discrepancies are caused by a wide range of factors.On the other hand,TCM/HM containing hundreds of chemically different constituents exhibit synergistic effects by multiple compounds toward multiple targets.Thus,these characteristics pose great challenges to comprehensive and effective TCM/HM quality control Compound Bismuth Aluminate Tablet(CBAT)contains not only three synthetic drugs,but also three medicinal herbs:Extract Licorice,Cortex Frangulae and Fructus Foeniculi.In this present paper,the quality control methods regarding HM in Compound Bismuth Aluminate Tablet were studied using multiple analytical means combined with chemometrics.The aim of the present study is to develop comprehensive,effective and feasible quality control method for the purpose of guaranteeing its safety and efficacy in clinical application.1.The index of the fingerprint information amount(I)was applied as an objective function to optimize the extraction and chromatography conditions,and a single wavelength HPLC fingerprinting at 250 nm was developed and applied to monitor the quality consistency of HM in CBAT.Simple quantified ratio fingerprint method was established for comprehensive quality discrimination of TCM/HM from qualitative and quantitative perspectives,by which the quality grades of 27 samples from the same manufacturer were well differentiated.In addition,Fenton reaction was applied to investigated the antioxidant activities in vitro of CBAT samples,and the fingerprint-efficacy relationship between fingerprints and antioxidant activities was established using partial least squares regression(PLSR),which provided important medicinal efficacy information for quality control.In summary,the method of a signal wavelength fingerprinting combined with fingerprint-efficacy relationship has been proved to be a feasible and simple procedure for monitoring the quality consistency of CBAT for manufacturers2.The index of the fingerprint information amount(I)was applied as an objective function to optimize the extraction and chromatography conditions,and a combination method of multi-wavelength fingerprinting and multi-component quantification by HPLC-DAD was developed to monitor the quality consistency of HM in CBAT.In order to combine the comprehensive characterization of multi-wavelength fingerprints,an integrated fingerprint assessment strategy based on information entropy was set up involving a super-information characteristic digitized parameter of fingerprints,which reveals the total entropy value and absolute information amount about the fingerprints and,thus,offers an excellent method for fingerprint integration.The simple quantified ratio fingerprint method was recommended to assess the quality of 27 CBAT samples,which has an important quantified fingerprint advantage over the 'Similarity' approach.The correlation analysis between quantified fingerprints and quantitative determination of five marker compounds,including glycyrrhizic acid(GLY),liquiritin(LQ),isoliquiritigenin(ILG),isoliquiritin(ILQ)and isoliquiritin apioside(ILA)was performed,the result indicated that multi-component quantification could be replaced by quantified fingerprints.The present study offered a new method for monitoring CBAT quality consistency.3.Micellar electrokinetic chromatography(MEKC)fingerprinting combined with two-component quantification was developed to monitor the quality consistency of CBAT.Background electrolyte(BGE)was optimized as follows.First,the most important factors influencing sample electrophoretic behavior were identified as background electrolyte concentrations.Then,a Box-Benhnken design response surface strategy using resolution index RF as an integrated response was set up to correlate factors with response.BGE composed of 57 mmol/L Na2B4O7,21 mmol/L SDS and 100 mmol/L NaOH was efficiently obtained with the assistance of multivariate statistical analyses.The quality of 27 samples was evaluated by Simple quantified ratio fingerprint method.In addition,the fingerprint-efficacy relationship between MEKC fingerprints and antioxidant activities was established using PLSR,and the obtained calibration model exhibited good predictive ability,which provided important medicinal efficacy information for quality control.It has been demonstrated that the present study offered a feasible and effective analytical strategy for CBAT quality control.4.The principle of systematic fingerprint quantification method(SFQM)was indicated and key parameters were elaborated.The quality grades of 27 CBAT samples were assessed by SFQM from qualitative and quantitative perspectives.Infrared(IR)and ultraviolet(UV)spectroscopy techniques as simple and rapid analytical means were implemented to establish the IR fingerprints and UV fingerprints for monitoring the quality consistency of CBAT.In order to combine the comprehensive chemical bond information of IR spectral fingerprints and UV spectral fingerprints,an integrated fingerprint assessment strategy of them was set up in equal weights,which offered a simple,rapid and comprehensive strategy.5.An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF)method was developed and applied to analyse the HM components in CBAT.A total of 23 compounds were tentatively identified based on accurate molecular weight,mass spectral fragmentation patterns,elution order or confirmed using standards.Semi-quantitative analysis method for 8 prototype components using rutin as an internal standard was developed by ultra-high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)and their dynamic changes in rat plasma were investigated after oral administration.The present study provided a reference for CBAT efficacy substance base and pharmacokinetics research.