Application Of Near Infrared And Mid Infrared Spectroscopy In The Extraction Process Control Of Xiao’er Xiaoji Zhike Oral Liquid

The production process of Traditional Chinese medicine(TCM)is complicated.At present,the production of TCM is carried out in accordance with the inherent technological parameters.The quality of drugs only relies on the traditional analysis method to carry out terminal detection,which is time-consuming,lacking in real-time and quality control of the production process.Therefore,the quality control and evaluation of TCM is one of the key problems restricting the modernization of TCM.The extraction process,as the main link of the separation of effective components of TCM,directly affects the subsequent production process and the quality of the final drug.Good manufacture practices(GMP)restrict the temperature,time and solvent dosage of the extraction process,hoping to control the quality of the process.The extraction process of compound Chinese medicine is a complex dynamic system with many variables and large disturbance.Process analysis technology can realize rapid monitoring of TCM production process and ensure the safety,effectiveness,stability and uniformity of final drug.In this study,the extraction process of Xiao’er Xiaoji Zhike Oral Liquid(XXZOL)was taken as the research object.Aiming at the lack of process quality control in the extraction process of traditional Chinese medicine compound preparation,two process analysis techniques(PAT)were discussed:near infrared spectroscopy(NIRS)and mid infrared spectroscopy(MIRS).The feasibility of application of NIRS and MIRS combined with chemometrics in the extraction of compound Chinese medicine is mainly studied,which provides a reference technology for monitoring the extraction process of XXZOL and improving the quality of medicine.The main research contents include the following three parts:(1)Determination of key quality markers in the extraction process of XXZOL by HPLC methodA HPLC method for simultaneous determination of 7 critical quality attributes(CQAs):syneferine,arecoline,chlorogenic acid,forsythione glycoside A,naringin,hesperidin and neohesperidin in the extract of XXZOL was developed.The method is simple,accurate,reliable and reproducible,and can be used to monitor the content changes of the above 7 CQAs during extraction process of XXZOL.In this study,the extraction process was simulated by pilot-scale sampling at intervals during the process.The experiment was repeated for 5 times and a total of 354 samples were collected.The HPLC method was used to determine the content values of 7 target components in all the extracted liquid samples,and the content change curve of each component in the extraction process was obtained,which also provided primary data reference for rapid quality control in the extraction process.(2)Study on quality control of the extraction process of XXZOL by NIRS and MIRSIn view of the lack of effective process analysis methods for the extraction process of XXZOL,two PAT were applied in this study.NIRS and MIRS of 354 extract samples were collected in transmission mode.Chemometrics was used to correlate the spectra with the content data in Chapter 1.Based on partial least squares regression(PLSR)method,NIRS and MIRS quantitative analysis models were established for syneferine,arecoline,chlorogenic acid,forsythione glycoside A,naringin,hesperidin and neohesperidin,respectively.The results indicated that both NIRS and MIRS methods could satisfy the needs of rapid determination of the contents of each CQAs in the extraction process of XXZOL.The performance of NIRS quantitative models were better than MIRS quantitative models,which provided reference for the quality control of the extraction process of XXZOL.(3)Study on quality control of the extraction process of XXZOL by data fusion strategyTo control the quality from multiple levels and dimensions and further enhance the accuracy of the model,this study established PLSR quantitative models for the extraction process of XXZOL based on NIR and MIR spectral data by using data fusion strategy.Four data fusion models(equal-weight fusion,external product fusion,feature band fusion and feature principal component fusion)were compared to predict the content of 7 7 CQAs during extraction process of XXZOL.The results showed that the prediction accuracy and model robustness of the feature band fusion models were the best,and the performance of the feature band fusion model is better than that of the single spectral model(NIRS model and MIRS model),especially for the low concentration component model.It provided a reference method with higher accuracy for the determination of substance content in Chinese herbal compound preparations,especially for the determination of 7 CQAs in the extract of XXZOL,which is of great significance for the development of quality analyzer of Chinese herbal compound preparations.