Application Of Second-order Calibration Methods Coupled With Analytical Instruments Such As LC-DAD And EEM For Quantitative Analysis Of Drug And Food Samples

With the rapid development of modern analytical instruments and the increasing complexity of analytical objects,modern analytical chemistry is facing enormous challenges as well as broad development opportunities,and Chemometrics emerged as a new subject to solve this problem.Multi-way data analysis and tensorial calibration have become attractive research fields.The second-order calibration methods has a unique "second-order advantage",which can realize quantitative analysis of multi-objective analytes in complex matrix under the condition of unknown interference(s)coexistence simultaneously.This strategy has been widely applied in biomedicine,food,environment and other fields,and are gaining widespread acceptance in the world.And in this paper,the author combined the modern second-order analysis instruments with the second-order calibration methods,and applied it to the research of food quality safety and drug quantitative analysis.The main contents are as follows:In Chapter 2: A methodology for simultaneously measuring seventeen polyphenols in six Chinese raw propolis samples by using chemometrics-assisted high performance liquid chromatography-diode array detection(HPLC-DAD)was developed and validated.With the aid of a second-order calibration method based on an alternating trilinear decomposition(ATLD)algorithm,HPLC analysis was easily achieved within 16.5 min even in the existence of heavily overlapped peaks and unknown interferences.The average recoveries were in the range of 95.2% to 118.7%with standard deviation less than 7.0% for the selected raw propolis.Figures of merit including sensitivity(SEN),selectivity(SEL),root mean square errors of prediction(RMSEPs),etc.were calculated to validate the accuracy of the proposed method.For further confirmation,a multiple reaction monitoring(MRM)method based on LC-MS/MS was adopted.The paired F-test and t-test results showed that there was no significant difference between the MRM and the proposed method at the 95%confidence level,which indicated that the developed ATLD-assisted HPLC-DAD method is a suitable tool for the rapid analysis of Chinese raw propolis.Considering its advantages of simplicity,rapidity,precision and accuracy,it might also be extended as an alternative and available method for the quality monitoring of propolis raw material in the pharmaceutical industry.In Chapter 3: Sulfonamides and quinolones are widely used in the treatment of human and animal diseases,and they have a broad spectrum of antibacterial activityand strong antibacterial activity.However,the abuse of multiple antibiotics threatens human health seriously.In this work,an excitation emission matrix fluorescence(EEM)combined with second-order calibration methods based on parallel factor analysis(PARAFAC)algorithm and self-weighted alternating trilinear decomposition(SWATLD)algorithm was developed for simultaneous quantitative analysis of sulfaguanidine(SGN),flumequine(FMQ)and marbofloxacin(MFX)in honey complex samples.With the help of its unique "second-order advantage",the pure spectral information of the target analytes was successfully extracted from complex three-dimensional fluorescence matrix data.The simultaneous quantitative analysis of multiple components was realized under the condition of serious spectral overlap and coexistence of background interference(s).The results show that the method has the advantages of simplicity,rapidity and sensitivity.It can be used for simultaneous detection of three kinds of antibiotics in honey complex background,and can also be developed as a new method for food analysis of pesticide residues.In Chapter 4: The oral anticoagulant dabigatran etexilate(DABE)is metabolized by enzymatic hydrolysis in vivo to form its active metabolite dabigatran(DAB)and achieves its efficacy,and it is necessary to measure their concentration in clinical settings.In this paper,a simple,rapid and accurate method was used for the simultaneous quantitative analysis of DABE and DAB in biological fluids by using excitation-emission matrix fluorescence(EEM)coupled with second-order calibration based on self-weighted alternating normalized residue fitting(SWANRF)algorithm.To overcome the poor selectivity of conventional fluorescence spectrophotometry,“mathematical separation” was skillfully used as a substitute for “physical or chemical separation” with the aid of Second-order Calibration Methods.Satisfactory results were successfully obtained for spiked plasma and urine samples even in the case of unknown interferences and serious spectral overlap.The average recoveries of DABE and DAB were 100.6% and 98.4% in plasma samples,and 91.0% and 95.2% in urine samples,respectively.Figures of merit(FOMs)and intra-and inter-day precision were also calculated to assess the performance of the proposed method,illustrating that it can be extensively utilized as a simple,fast,green,high-efficiency and universal strategy for the determination of clinical drugs.