Guoxiang Sun

Capillary electrophoresis fingerprinting coupled with chemometrics to evaluate the quality consistency and predict the antioxidant activity of Sanhuang tablet as part of its quality control

A capillary electrophoresis fingerprint was constructed for Sanhuang tablet, a Chinese traditional patent medicine, that was commonly used in clinical practice, where the isosceles trapezoid method was first applied for the optimization of background electrolyte solution, and the resolution index was performed to assess the experimental conditions; furthermore, a novel linear quantitative fingerprint method was established for accurate qualitative and quantitative discrimination of the test samples from diverse commercial brands. The fingerprint analysis coupled with quantitative determination of two components was employed to elucidate that the quality consistency of the products was relatively good within one manufactory, but poor among different companies for the 30 batches of samples. In addition, the fingerprint-efficacy relationship between chemical components and antioxidant activity in vitro was investigated using partial least squares analysis, and the calibration and prediction of the antioxidant activity of the selected samples via fingerprint data were presented with the desired results. This work illustrates that the proposed fingerprint analysis based on linear quantitative fingerprint method can be applied for the quality evaluation of traditional Chinese medicine and herbal preparations as part of their quality control, and the constructed mathematical model is particularly suitable for depicting the fingerprint-efficacy relationship.

Multiple methods were combined to monitor and evaluate the quality of TCM, and make the results more reliable

A high performance liquid chromatography (HPLC) method with diode array detector (DAD) was developed and validated for multi-wavelength fingerprint profiling to evaluate the quality consistency of a Traditional Chinese Medicine, Fangfeng Pill. The validation results demonstrate that the optimized HPLC method achieves the desired linearity, precision, accuracy, LOQ and LOD. The multi-wavelength fingerprints were developed and qualitatively and quantitatively evaluated using the Ratio Fingerprint Quantification Method (RFQM). The fingerprint analysis of the marker compounds (baicalin, wogonin, glycyrrhizic acid, baicalein, paeoniflorin, gardenoside, and ephedrine) was found to reflect the content of the marker compounds in the Fangfeng Pill samples determined using the external standard method. The classical Fenton reaction was performed to assess the antioxidant activity of the Fangfeng Pill samples in vitro, which was correlated to the fingerprint components. This study demonstrates that multi-wavelength fingerprint profiling correlated the antioxidant activity offering a reliable and efficient approach to quantitatively evaluate the quality consistency of the TCM and herbal preparations.

Hierarchical polystyrene@reduced graphene oxide–Pt core–shell microspheres for non-enzymatic detection of hydrogen peroxide

A non-enzymatic electrochemical sensor based on polystyrene@reduced graphene oxide (RGO)–Pt core–shell microspheres was developed for sensitive detection of hydrogen peroxide (H2O2). The polystyrene@RGO–Pt microspheres were prepared by microwave-assisted reduction of graphene oxide (GO) and a Pt precursor (H2PtCl6) that were adsorbed on polystyrene microspheres. No surfactants or polyelectrolytes were used as stabilizing agents for the preparation of the nanocomposite. Alternatively, polystyrene microspheres served as the core for supporting RGO nanosheets and Pt nanoparticles, which prevented the aggregation of the electrode material and resulted in the high electrochemically active surface area. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-vis absorption spectroscopy (UV), and Brunauer–Emmett–Teller (BET) measurements characterized the nanostructure of the polystyrene@RGO–Pt microspheres. Cyclic voltammetry revealed the enhanced electrocatalytic activity of these core–shell microspheres. Such a non-enzymatic electrochemical sensor is capable of detecting H2O2 with a wide linear range (0.5 μM–8000 μM), high sensitivity (38.57 μA mM−1 cm−2), low detection limit (0.1 μM, S/N = 3), long-term stability, and good selectivity. Furthermore, this sensor was found to be suitable for the determination of H2O2 in human serum samples. Considering their simple synthetic procedure and high catalytic activity, the polystyrene@RGO–Pt microspheres hold great promise in the development of high performance electrochemical sensors.

Holistic Evaluation of Quality Consistency of Ixeris sonchifolia (Bunge) Hance Injectables by Quantitative Fingerprinting in Combination with Antioxidant Activity and Chemometric Methods

A widely used herbal medicine, Ixeris sonchifolia (Bge.) Hance Injectable (ISHI) was investigated for quality consistency. Characteristic fingerprints of 23 batches of the ISHI samples were generated at five wavelengths and evaluated by the systematic quantitative fingerprint method (SQFM) as well as simultaneous analysis of the content of seven marker compounds. Chemometric methods, i.e., support vector machine (SVM) and principal component analysis (PCA) were performed to assist in fingerprint evaluation of the ISHI samples. Qualitative classification of the ISHI samples by SVM was consistent with PCA, and in agreement with the quantitative evaluation by SQFM. In addition, the antioxidant activities of the ISHI samples were determined by both the off-line and on-line DPPH (2, 2-diphenyl-1-picryldrazyl) radical scavenging assays. A fingerprint–efficacy relationship linking the chemical components and in vitro antioxidant activity was established and validated using the partial least squares (PLS) and orthogonal projection to latent structures (OPLS) models; and the online DPPH assay further revealed those components that had position contribution to the total antioxidant activity. Therefore, the combined use of the chemometric methods, quantitative fingerprint evaluation by SQFM, and multiple marker compound analysis in conjunction with the assay of antioxidant activity provides a powerful and holistic approach to evaluate quality consistency of herbal medicines and their preparations.

Monitoring and Evaluating the Quality Consistency of Compound Bismuth Aluminate Tablets by a Simple Quantified Ratio Fingerprint Method Combined with Simultaneous Determination of Five Compounds and Correlated with Antioxidant Activities

A combination method of multi-wavelength fingerprinting and multi-component quantification by high performance liquid chromatography (HPLC) coupled with diode array detector (DAD) was developed and validated to monitor and evaluate the quality consistency of herbal medicines (HM) in the classical preparation Compound Bismuth Aluminate tablets (CBAT). The validation results demonstrated that our method met the requirements of fingerprint analysis and quantification analysis with suitable linearity, precision, accuracy, limits of detection (LOD) and limits of quantification (LOQ). In the fingerprint assessments, rather than using conventional qualitative “Similarity” as a criterion, the simple quantified ratio fingerprint method (SQRFM) was recommended, which has an important quantified fingerprint advantage over the “Similarity” approach. SQRFM qualitatively and quantitatively offers the scientific criteria for traditional Chinese medicines (TCM)/HM quality pyramid and warning gate in terms of three parameters. 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 correlation results between quantified fingerprints and quantitative determination of 5 marker compounds, including glycyrrhizic acid (GLY), liquiritin (LQ), isoliquiritigenin (ILG), isoliquiritin (ILQ) and isoliquiritin apioside (ILA), indicated that multi-component quantification could be replaced by quantified fingerprints. The Fenton reaction was employed to determine the antioxidant activities of CBAT samples in vitro, and they were correlated with HPLC fingerprint components using the partial least squares regression (PLSR) method. In summary, the method of multi-wavelength fingerprints combined with antioxidant activities has been proved to be a feasible and scientific procedure for monitoring and evaluating the quality consistency of CBAT.

Integrated evaluation of HPLC and UV fingerprints for the quality control of Danshen tablet by systematic quantified fingerprint method combined with antioxidant activity

Danshen tablet, which consists of Salviae Miltiorrhizae Radix et Rhizoma, Notoginseng Radix et Rhizoma and Borneolum syntheticum, has been widely used in the therapy of cardiovascular disease. The aim of this study was to develop comprehensive evaluation methods for the quality control of Danshen tablet. First, five-wavelength fusion fingerprint was established to avoid one-sidedness of a single wavelength. Then, the ultraviolet spectrum fingerprint was applied to reflect the information of unsaturated bond and conjugated system of chemical substances in Danshen tablet. The similarity analyses of these two fingerprints were performed by systematic quantified fingerprint method in terms of qualitative and quantitative aspects. After that, the evaluation results of high-performance liquid chromatography and ultraviolet fingerprints were integrated by the mean algorithm, which could reduce the error caused by single method. The integrated evaluation results showed that 30 batches of samples were classified into seven grades. Finally, the fingerprint-efficacy relationship was established using an on-line antioxidant system and partial least-squares model to explore the connection between chemical components and antioxidant activities. The methods established in this paper were found suitable for the analysis of Danshen tablet.

A comprehensive strategy to monitor quality consistency of Weibizhi tablets based on integrated MIR and UV spectroscopic fingerprints, a systematically quantified fingerprint method, antioxidant activities and UPLC-Q-TOF-MS chemical profiling

As complicated mixture systems, traditional Chinese medicines (TCM)/herbal medicines (HM) are very difficult to comprehensively investigate with regard to their quality consistency by chromatographic fingerprinting using a single detection technique. Therefore, finding a rapid, effective and comprehensive quality control method is of great importance for guaranteeing TCM/HM safety and efficacy in clinical applications. In this research, a novel combination strategy of mid-infrared (MIR) and ultra violet (UV) spectroscopic fingerprinting using Fourier transform mid-infrared (FTMIR) spectrometry and flow injection analysis (FIA) was developed and applied to monitor the quality consistency of HM in popular patent drug Weibizhi tablets (WBZT). In order to completely identify saturated and unsaturated chemical bonds for HM components in WBZT, an integrated assessment method based on MIR and UV spectroscopic fingerprinting was set up. The quality grades of 27 batches of WBZT samples from the same manufacturer were successfully discriminated by means of a systematically quantified fingerprint method (SQFM), in which both qualitative and quantitative evaluation parameters were scientifically improved on the basis of ‘Similarity’ conventionally used and ‘simple quantified ratio fingerprint method’ previously proposed. In addition, the HM chemical profiling of WBZT samples was obtained by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in positive ion mode, providing an important chemical structure foundation for further bioactivity and quality control studies. The relationship between high performance liquid chromatography (HPLC) fingerprints and antioxidant activities of WBZT samples was established using the partial least squares regression (PLSR) method, which offers a robust predictive ability of the antioxidant activities of WBZT samples. This study demonstrates that integrated MIR and UV spectroscopic fingerprints combined with antioxidant activities can monitor TCM/HM quality consistency rapidly, effectively and comprehensively.

Microemulsion Electrokinetic Chromatography in Combination with Chemometric Methods to Evaluate the Holistic Quality Consistency and Predict the Antioxidant Activity of Ixeris sonchifolia (Bunge) Hance Injection

In this paper, microemulsion electrokinetic chromatography (MEEKC) fingerprints combined with quantification were successfully developed to monitor the holistic quality consistency of Ixeris sonchifolia (Bge.) Hance Injection (ISHI). ISHI is a Chinese traditional patent medicine used for its anti-inflammatory and hemostatic effects. The effects of five crucial experimental variables on MEEKC were optimized by the central composite design. Under the optimized conditions, the MEEKC fingerprints of 28 ISHIs were developed. Quantitative determination of seven marker compounds was employed simultaneously, then 28 batches of samples from two manufacturers were clearly divided into two clusters by the principal component analysis. In fingerprint assessments, a systematic quantitative fingerprint method was established for the holistic quality consistency evaluation of ISHI from qualitative and quantitative perspectives, by which the qualities of 28 samples were well differentiated. In addition, the fingerprint—efficacy relationship between the fingerprints and the antioxidant activities was established utilizing orthogonal projection to latent structures, which provided important medicinal efficacy information for quality control. The present study offered a powerful and holistic approach to evaluating the quality consistency of herbal medicines and their preparations.

Monitoring the quality consistency of Fufang Danshen Pills using Micellar electrokinetic chromatography fingerprint coupled with prediction of antioxidant activity and Chemometrics

A fast micellar electrokinetic chromatography fingerprint method combined with quantification was developed and validated to evaluate the quality of Fufang Danshen Pills, a traditional Chinese Medicine, which has been used in the treatment of cardiovascular system diseases, in which the tetrahedron optimization method was first used to optimize the background electrolyte solution. Subsequently, the index of the fingerprint information amount of I was performed as an excellent objective indictor to investigate the experimental conditions. In addition, a systematical quantified fingerprint method was constructed for evaluating the quality consistency of 20 batches of test samples obtained from the same drug manufacturer. The fingerprint analysis combined with quantitative determination of two components showed that the quality consistency of the test samples was quite good within the same commercial brand. Furthermore, the partial least squares model analysis was used to explore the fingerprint-efficacy relationship between active components and antioxidant activity in vitro, which can be applied for the assessment of anti-oxidant activity of Fufang Danshen pills and provide valuable medicinal information for quality control. The result illustrated that the present study provided a reliable and reasonable method for monitoring the quality consistency of Fufang Danshen pills.

Monitoring the quality consistency of Weibizhi tablets by micellar electrokinetic chromatography fingerprints combined with multivariate statistical analyses, the simple quantified ratio fingerprint method, and the fingerprint–efficacy relationship

Micellar electrokinetic chromatography fingerprinting combined with quantification was successfully developed and applied to monitor the quality consistency of Weibizhi tablets, which is a classical compound preparation used to treat gastric ulcers. A background electrolyte composed of 57 mmol/L sodium borate, 21 mmol/L sodium dodecylsulfate and 100 mmol/L sodium hydroxide was used to separate compounds. To optimize capillary electrophoresis conditions, multivariate statistical analyses were applied. 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. RF reflects the effective signal amount, resolution, and signal homogenization in an electropherogram, thus, it was regarded as an excellent indicator. In fingerprint assessments, simple quantified ratio fingerprint method was established for comprehensive quality discrimination of traditional Chinese medicines/herbal medicines from qualitative and quantitative perspectives, by which the quality of 27 samples from the same manufacturer were well differentiated. In addition, the fingerprint-efficacy relationship between fingerprints and antioxidant activities was established using partial least squares regression, which provided important medicinal efficacy information for quality control. The present study offered an efficient means for monitoring Weibizhi tablet quality consistency.