HPLC-DAD And EEM Combined With Second-order Calibration For Quantitative Research Of Multiple Drugs In Complex Systems

In recent years,chemometrics multivariate calibration has been widely used in a variety of technologies and fields,such as biology,medicine,environment,food and other popular fields.Successfully used mathematical separation to quickly solve many complex problems.Because of the"second-order advantage",it can simultaneously perform rapid and accurate quantification of multiple target analytes under the presence of multiple unknown interferences in complex matrices.In this paper,the author combined the multivariate calibration methods and the high-order analytical instrument to carry out the accurate quantitative analysis and research on various drugs in the traditional Chinese medicine,environment and biological system.At the same time,the performance of the methods were evaluated.The content of this paper is mainly divided into the following three parts:In Chapter 2:Wen-Qing-Yin（WQY）is a traditional Chinese medicine（TCM）formula,which is composed of Huang Lian Jie Du Tang and Si Wu Tang,including Radix Angelicae Sinensis,Radix Paeoniae Alba,Radix Rehmanniae Praeparata,Rhizoma Chuanxiong,Rhizoma Coptidis,Radix Scutellaria,Cortex Phellodendri and Fructus Gardeniae.For the treatment of gynecological bleeding disorders,skin diseases,recurrent aphthous ulcer,etc.TCM contains multiple components,and the content of active components will affect its quality.Therefore,it is very important to develop appropriate methods to monitor the content of active constituents in TCM.In this Chapter,a simple analytical strategy combining high-performance liquid chromatography-diode array detection（HPLC-DAD）and chemometrics methods were developed for the simultaneously quantification of hydroxymethyl furfural（HMF）,paeoniflorin（PAE）,ferulic acid（FER）,baicalin（BAI）and berberine（BER）in a Chinese medicine formula Wen-Qing-Yin（WQY）.The alternating trilinear decomposition（ATLD）algorithm and alternating trilinear decomposition assisted multivariate curve resolution（ATLD-MCR）algorithm were used to realize the separation and rapid determination of five target analytes under the presence of time shifts,solvent peaks,peak overlaps,and unknown interferences.All analytes were eluted within 10 min and the linear correlation coefficients of calibration sets were between 0.9969-0.9996.In addition,the average recoveries of the five active compounds obtained by ATLD and ATLD-MCR analysis were in the range of91.8-112.5%and 88.6-101.6%.For investigating the accuracy and reliability of the proposed method,figures of merit including limit of detection（LOD）,limit of quantitation（LOQ）,sensitivity（SEN）and selectivity（SEL）were calculated.The proposed analytical strategy has the advantages of being fast,simple,sensitive,and can be used for the qualitative and quantitative analysis of WQY,providing a feasible option for the quality monitoring of traditional Chinese medicine formulae.In Chapter 3:Benomyl is a carbamate fungicide,and carbaryl is a carbamate insecticide.Both are widely used in agricultural production.At present,chemical pollution caused by various pesticides has been affecting our ecosystem for a long time,especially when the level of pesticides in the soil will continue to accumulate over time,causing serious soil pollution problems.At the same time,their presence in the environment may cause serious harm to biological and human health.Therefore,it is necessary to develop fast,sensitive and accurate analytical methods that can determine the level of pesticide residues in environmental soils.In this chapter,a strategy for assisting excitation-emission matrix fluorescence spectroscopy with a multivariate calibration method in chemometrics is developed.The simultaneous quantification of carbaryl and benomyl in soil sample was achieved.The recovery rates of the two pesticides in the soil matrice ranged from 98.9%-102.6%,and the relative standard deviations were less than 8.9%.The value of the correlation coefficient is between 0.9977-0.9984.At the same time,the detection limit range was1.28-6.43 ng m L^-1.Figures of merit such as limit of quantification,sensitivity and selectivity,as well as intra-day and inter-day precision are also satisfactory.The results show that even if the interference caused by soil backgrounds is serious,the fluorescence of the two substances also has a serious overlap.This strategy can still achieve rapid and accurate quantitative detection of them,and can be used as a powerful monitoring tool for pesticide detection in the environment.In Chapter 4:Terbutaline（TEB）is a beta2-adrenergic receptor agonist,and montelukast（MKT）is one of the leukotriene receptor antagonists,both of which are used to treat asthma.Moreover,the combination of MKT and TEB has a good therapeutic effect on cough variant asthma in children and bronchial asthma commonly occurring in the elderly population.The widespread use of these two drugs requires accurate and precise clinical monitoring,as well as better analysis of their efficacy.Therefore,it is necessary to develop a rapid,economical,and accurate method for simultaneous quantification of these two drugs.The strategy presented in this chapter utilizes EEM data combined with stoichiometric tools for sensitive and rapid quantification of terbutalin and montelukast in the context of complex background interference from human plasma samples.The Excitation-emission matrix fluorescence data were analyzed by ATLD algorithm,and satisfactory quantitative analysis results were obtained under the interference of fluorescence peak overlap and plasma matrix.The correlation coefficients of TEB and MKT were above 0.99,and the average recoveries were（101.0±2.4）%and（98.5±4.3）%,respectively.At the same time,the figures of merit of this method and the precision of repeatability and reproducibility were evaluated,all the results were satisfactory.In general,the method proposed in this chapter is sensitive and accurate,with low analysis cost,fast analysis speed and simple pretreatment.It can not only realize the rapid quantitative detection of these two asthma drugs in human plasma,but also is expected to improve the speed and accuracy of diagnosis in the application of these two drugs in clinical diagnosis and drug monitoring.