Application Of Near Infrared Spectroscopy In Quality Analysis Of Xinkeshu Tablet

Xinkeshu Tablet(XKS)is a kind of traditional Chinese medicine(TCM),with the function of activating blood,removing stasis and relieving pain.It is mainly used for various cardiovascular diseases,which is proved to be an effective cure and widely used in clinical treatment.According to the basic principle of prescription compatibility,it is composed of five Chinese medicines,including the monarch drug Salvia miltiorrhiza(S.miltiorrhiza),the minister drug notoginseng and Radix puerariae,the assistant drug Radix aucklandiae and the envoy drug Hawthorn.Among them,the monarch drug S.miltiorrhiza plays the main therapeutic role in the prescription,and reflects the main function of the prescription,which is indispensable with the most efficacy.In the current research for S.miltiorrhiza and XKS,the high performance liquid chromatography(HPLC)is the most commonly used to assess the quality of active components.However,the method requires complicated sample pretreatment before measurement,takes a long time and is unfriendly to environment,which is not conducive to the quality,control in actual production and procurement process of enterprises.In recent years,the near infrared spectroscopy(NIRS)has been widely used in many aspects of quality evaluation of TCM,such as discrimination of origins and quantification of active components due to the speed of analysis,minimal sample preparation and low cost.At the same time,the portable NIR spectrometers,with the merits of higher efficiency,on-site testing ability,small size and portability,have attracted much attention and are very appropriate for on-site detection and quality analysis in the procurement of raw materials for pharmaceutical production.With the application and development of NIRS,chemometrics has become an important part of NIRS research and should be developed continuously.Referring to the literature,there were still few studies on the application of NIRS in S.miltiorrhiza and XKS.And it’s not clear that if the prediction results of portable NIR spectrometers can achieve the equal performance to that of conventional analytical-grade NIR spectrometers.Moreover,the problem of model failure is frequent in practical application.Up to now,the non-invasive detection of TCM like XKS by NIRS wasn’t carried out.Based on the above problems,this paper focused on the quality analysis and evaluation of S.miltiorrhiza and XKS by NIRS technique,the main research content included the following aspects:1.Comparative analysis of rapid quality evaluation of S.miltiorrhiza with Fourier transform near infrared spectrometer and portable near infrared spectrometerA Fourier transform NIR spectrometer and a portable NIR spectrometer were both employed to collect the spectra of 120 S.miltiorrhiza samples.The geographical origins were discriminated by using partial least squares-discriminant analysis(PLS-DA)and the satisfactory discrimination results can be obtained by both instruments.PLS regression was applied to establish the quantification models for 4 active components(ACs)and antioxidant activity(AA)by NIRS.The ACs included tanshinone Ⅱ A,cryptotanshinone,tanshinone Ⅰ and salvianolic acid B.The correlation coefficients in the prediction set(Rp2)of Fourier transform near infrared spectroscopy(FT-NIRS)models for all ACs were above 0.93 with small root-mean square errors of validation(RMSEP)and residual prediction deviation(RPD)values all greater than 3.While the micro near infrared spectroscopy(MicroNIRS)models performed slightly worse:the Rp2 values for most components can reach 0.92 with RPD values higher than 3,which was still enough for prediction,but for cryptotanshinone,the prediction error was larger and it may be difficult to guarantee accurate prediction results with limited samples.In the prediction of AA,since the reference values of AA were influenced by reaction contingency and experimental manipulation,several variable selection methods were then used to improve the evaluation of AA,and the RPD value of FT-NIRS can be increased from 3.3 to 4.1.while the MicroNIRS model became worse after variable selection due to the limited number of spectral variables and low resolution.According to the comparative analysis of the two instruments,this study could provide a useful reference and basis for instrument performance and accessible accuracy when performing rapid quality analysis of S.miltiorrhiza by NIRS.2.A sample selection method specific to unknown test samples for calibration and validation sets based on spectra similarityA method was proposed for the calibration and validation sets constructed by selecting samples maximally similar to the test samples based on the spectra data.Both the Euclidean distance and Mahalanobis distance were attempted to estimate the spectra similarity.The method to select samples for calibration is more suitable and specific to unknown test samples in practical applications,thus improving the measurement accuracy.In addition,the optimization of calibration set size was carried out to avoid the influence of unnecessary samples.Two data sets of S.miltiorrhiza and corn by NIRS were used to test the performance of the proposed method compared with two typical sample-selection algorithms,Kennard-Stone(KS)and sample set partitioning based on joint x-y distances(SPXY).The experimental results indicated that the proposed method could select a more targeted set of samples for the unknown test samples and had the superior predictive performance to the KS and SPXY methods.In addition,when the calibration model can’t cover the space of unknown test samples and the prediction results were not accurate,the method can be used for model updating and maintenance.3.Research on non-invasive,rapid and non-destructive detection method of Xinkeshu Tablet by NIRSThe PLS quantitative models of sodium Danshensu,protocatechualdehyde,puerarin and salvianolic acid B in Aluminum-plastic packed Xinkeshu Tablets were established,respectively.And the optimization effects of different pretreatments were compared.Meanwhile,different concentrations of Xinkeshu Tablet solution were prepared by diluting or adding reference substance,the quantitative models of Xinkeshu Tablet solution were established as well.Compared with the Aluminum-plastic packaging tablet models,the prediction performance of solution models were significantly improved,which may be related to the uniformity and stability and a wider concentration range of solution.Taking sodium Danshensu as an example,Slope Bias Correction(SBC)was employed to correlate the model of Aluminum-plastic packaging tablet by solution model,thus improving the prediction accuracy.The experimental results showed that the SBC method can improve the prediction results of the PLS model of Xinkeshu Tablet with Aluminum-plastic packaging,and can be used for non-in vasive and rapid quality evaluation of Xinkeshu Tablet.