| With the increasing complexity of the research system and the diversification of analytical instruments,researchers can easily obtain massive amounts of data.How to quickly and accurately capture,analyze,express and present useful chemical information about target analytes from complex massive data is the goal that analysts are committed to pursuing.In this context,chemometrics emerged as the times require.It aims to construct and develop higher-level and more efficient massive data analysis strategies through mathematical models,and obtain important and useful chemical information as quickly,comprehensively and accurately as possible.And convert information into knowledge to solve practical problems.Therefore,this thesis aims to explore the two major research hotspots of chemometrics—chemical multiway calibration and chemical pattern recognition,and to carry out relevant basic theory and basic application research,and to develop a series of green qualitative and quantitative analysis strategies.The research contents are as follows:Part Ⅰ: High-order analytical instruments combined with multi-way calibration methods for green and interference-free quantification of biological systems(Chapter 2-Chapter 3)In Chapter 2: A series of green,interference-free excitation-emission matrix fluorescence combined with three second-order calibration methods were proposed for the determination of ibrutinib and pralatrexate in four different biological matrices.The proposed method fully combines the "second-order advantage" of the second-order calibration methods and the high sensitivity advantage of the fluorescence method.Even for four different biological matrices,there is no need to explore and optimize conditions,and only one set of calibration sets is needed to achieve simultaneous and accurate quantitative analysis of multiple analytes in different complex matrices,which has the advantages of saving time,economy,environmental protection,and strong versatility.In addition,the proposed method was validated according to the “Guidelines for the Validation of Bioanalytical Methods” issued by the European Medicines Agency(EMA),and the accuracy of the three methods was further compared using elliptical confidence intervals.The results show that all three methods can achieve accurate quantification and can meet the actual clinical needs.Compared with published work,the proposed strategy features faster data acquisition(only 1.3 min per sample),simpler preprocessing steps,lower experimental cost and lower LOD,etc.,which is expected to provide a promising and alternative general analysis strategy for clinical drug monitoring.In Chapter 3: Intelligent second-order calibration methods assisted high performance liquid chromatography-diode array detector(HPLC-DAD)were used for the simultaneous quantitative analysis of ten molecular targeted anti-tumor drugs in three different biological matrices.Ten analytes were eluted within 6.5 minutes.Experimentally,each sample was found to have different levels of time shifts,so three common second-order calibration methods for dealing with time shifts(multivariate curve resolution-alternating least squares(MCR-ALS),alternating trilinear decomposition assisted multivariate curve resolution(ATLD-MCR)and alternating trilinear decomposition(ATLD))are used to analyze the data.The results show that all three methods can successfully process the chromatographic data with slight time shifts.But for the chromatographic data with large time shifts(e.g.5.6 s),only MCR-ALS and ATLD-MCR can obtain satisfactory results,while the results obtained by ATLD are not ideal.The figures of merit and statistical test were performed on the results of the two methods,and the results were consistent without significant differences.Both methods can more flexibly deal with chromatographic data with time shifts.Compared with published methods,for different biological matrices,ATLD-MCR or MCR-ALS assisted HPLC-DAD methods form a super separation analysis strategy of "physical/chemical separation + mathematical separation",which can directly measure the mixed response signals of all complex samples without re-exploration and optimization of chromatographic conditions.It allows simultaneous qualitative and quantitative analysis of target analytes under different unknown background interferences and overlapping peaks,which has the advantages of being simpler,faster and more flexible.The proposed strategy is expected to provide a basis for corresponding pharmacokinetic studies.Part Ⅱ: Research on the application of high-order analytical instruments combined with chemometric methods for accurate food identification(Chapter 4-Chapter 5)In Chapter 4: In view of the increasingly serious problem of mislabeling the origin of Atractylodes macrocephala Koidz.(AM)in Chin,a simple and rapid method,namely multi-way fluorescence fingerprinting combined with chemometrics methods,was proposed to classify AM from different geographical origins.Experiments found that AM samples with different dilution levels had different fluorescence characteristics,which may be caused by the different content of fluorescent components and chemical microenvironments.Hence,in order to acquire more abundant information,the AM samples were diluted 5-fold,10-fold,and 20-fold to obtain the corresponding excitationemission matrix data,and then the corresponding three-dimensional and fourdimensional data arrays were constructed.On the one hand,the fluorescence fingerprints of AM samples were characterized by three-dimensional and fourdimensional parallel factor analysis,respectively.On the other hand,four pattern recognition methods were employed to classify AM from different provinces.The results show that compared with the three-dimensional data array,the four-dimensional data array provides richer information and is more conducive to sample classification.The analysis results of the four-dimensional data array show that the correct classification rate of the cross-validation set,training set,test set and prediction set based on partial least squares-discriminant analysis(PLS-DA)are 90.5%,100%,96.7%and 100%,respectively.In summary,a feasible,fast,convenient and reliable method for geographical traceability of AM samples is proposed,which can be used as a general method to quickly identify the geographical traceability of other traditional Chinese medicines.In Chapter 5: The prices of different Wuyi rock tea(WRT)varieties vary greatly,and the confusion of varieties and unclear constituent differences are the main problems in the current market.Therefore,a whole-process chemometrics-assisted highperformance liquid chromatography-diode array detection strategy was proposed for targeted metabolites analysis and variety discrimination of WRT.The strategy involves four aspects: experimental design,quantification,varieties discrimination and differential component screening.Specifically,optimal extraction conditions of WRT are obtained by response surface methodology-Box-Behnken design method.Then,22 targeted metabolites are rapidly and accurately quantified by second-order calibration method with average spiked recoveries ranging from 85.4% to 108.6%.Finally,the four WRT varieties(110 samples)are discriminated by two pattern recognition methods(PLS-DA and LDA)with relative concentration results as model input.The correct classification rates obtained by PLS-DA are greater than 88%,especially for highquality “Niulankeng rougui” tea,its specificity and sensitivity are 100%.Finally,ten differential biomarkers related to identification are screened by variable importance in projection.In short,this work scientifically and comprehensively elaborates the wholeprocess of WRT variety identification and can also become a comprehensive food analysis strategy for the purpose of precise quantification and pattern recognition.Part Ⅲ: The extension of the basic theory of multi-way calibration method(Chapter 6)In Chapter 6: With the development of analytical instruments towards more and more high-way and complex,it is very important and meaningful work to obtain ultrahigh-way chemical data and explore its analytical methods.A novel and excellent sixway algorithm combination method(six-way ACM)was proposed.In addition,a real chemically meaningful ultra-high-way hexalinear six-way data array was obtained for the first time,and it is constructed by recording the excitation-emission matrix fluorescence data of different samples under different p H buffer solutions,dilution ratios and detection voltages.The proposed six-way data array has high collinearity,which puts forward higher requirements for parsing this data array to a certain extent.To verify the feasibility of the proposed algorithm,it was used to analyze the above real hexalinear six-way data array and a series of simulated six-way data arrays with different noise levels.The results of real data and simulated data demonstrate that the proposed method can be well used in the analysis of six-way data arrays,and shows fascinating performance,including insensitive to excessive number of components,fast convergence speed,and suitable for high collinearity and high noise data.Compared with three-way calibration method,higher sensitivity,lower limit of detection,lower limit of quantification,more stable and accurate results are obtained by the six-way ACM,showing outstanding “higher-order advantages” and better ability to handle collinearity problems.This work not only provides data analysis method for high-order instruments that may emerge in the future,but also provides real data support and methodological reference for theoretical research on high-order tensor algebra. |
