Differential Kinetic Spectrophotometric (Or Spectrofluorometric) Determination Of Some Substances In Complex Systems By Chemometrics

The research mainly aims at the rapid quantitative determination of complex multi-component system in food and drug. Meanwhile, an overview of the application of chemometrics methods to differential kinetic analysis in recent years was reviewed. Differential kinetic approaches involve similar species reacting with a common reagent or undergoing a common process, different kinetic rate in the reaction or process are observed and used to distinguish individual components without any physical preseparation. The chemometric techniques were useful for handling kinetic data to determine the analytes accurately. In the thesis, various chemometric approaches were applied to differential kinetic spectrophotometric determination of some substances in complex systems. This thesis is composed of five chapters.ChapterⅠ: In this chapter, the application of chemometrics methods to differential kinetic analysis for the aspects of food and drug was reviewed. H-point standard addition approach, derivative technique, multivariate linear regression approaches, multivariate calibration approaches based on factor analysis, artificial neural networks approaches, parallel factor method, n-way partial least squares are summarized and discussed. In addition, the prospects of chemometrics in differential kinetic analysis were also given.ChapterⅡ:A highly sensitive kinetic spectrophotometric method was developed for the determination of four flavor enhancers, maltol, ethyl maltol, vanillin and ethyl vanillin, in food samples. The method is based on the reduction of iron(Ⅲ) by the studied components in sulfuric acid medium (0.012 mol L-1) and subsequent interaction of iron(Ⅱ) with hexacyanoferrate(Ⅲ) to form Prussian blue, which exhibits absorption maximum at 800 nm. The optimized method was valid over the concentration ranges of 0.2-2.8,0.2-2.8, 0.2-1.8 and 0.2-1.8 mg L-1 for maltol, ethyl maltol, vanillin and ethyl vanillin respectively, and their corresponding detection limits were 0.07,0.07,0.06 and 0.06 mg L-1. The measured data were processed by two chemometrics methods, partial least squares (PLS) and principal component regression (PCR), using the normal and the first-derivative pretreatments. The proposed procedure was successively applied for the determination of the four compounds in commercial food samples and the results were comparable with those from a reference HPLC method.ChapterⅢ: An accurate, reliable, and simple kinetic spectrophotometric method was developed for the simultaneous determination of three cephalosporin antibiotics, cephradine, cefaclor and cefixime. This method relies on the different kinetic rates of the analytes in their oxidative reaction with KMnO4 to produce the green manganate product in an alkaline solution. Three chemometrics methods, principal component regression (PCR), partial least squares (PLS) and radial basis function-artificial neural networks (RBF-ANN), were used to resolve the measured data and better results were obtained by PLS model. This model was successfully applied to a pharmacokinetics of three cephalosporin antibiotics in rabbit plasma, and the quantitative results compared well with those obtained by HPLC method. The proposed method was applied to a pharmacokinetic study of intravenous analytes injections in rabbits.ChapterⅣ: A simple, sensitive, and accurate kinetic spectrophotometric method with the aid of chemometrics method was proposed for the determination of phentolamine and aramine. The method relies on the oxidative coupling of analytes to N,N-diethyl-p-phenylenediamine in the presence of hexacyanoferrate(Ⅲ). Calibration curves for the individual analytes showed linear relationships over the concentration ranges of 0.1-3.4 mg L-1 at 670 nm for phentolamine and 0.3-14.4 mg L-1 at 690nm for aramine, respectively. LODs for phentolamine and aramine are 0.04 and 0.13 mg L-1. Various multivariate calibration models were applied for the simultaneous prediction of the two analytes including parallel factor method (PARAFAC), n-way partial least squares (NPLS), partial least squares (PLS), principal component regression (PCR), radial basis function-artificial neural network (RBF-ANN) calibrations. The proposed method was applied for the simultaneous determination of the analytes in pharmaceutical and rabbit plasma samples, and the results were comparable with those from a reference HPLC method.ChapterⅤ:A highly sensitive and simple kinetic spectroflurometric approach was described for the simultaneous determination of sibutramine, indapaminde and hydrochlorothiazide in mass-reducing tonic samples. The method is based on the oxidation of the studied drug with cerium(Ⅳ) sulfate in acidic medium to form the fluorescence of Ce(lll), for which the fluorescence intensity was measured atλex=250nm andλem=355nm. Different variables affecting the kinetic resction system under study were carefully investigated and evaluated. Under the optimum conditions, the analytical kinetic curves gave linear range of 0.005-0.12 ing L-1 and a detection limit of 1.6×10-3 mg L-1 for sibutramine,0.03-1.44 mg L-1 and 8.3×10-3 mg L-1'for indapamide, and 0.01-0.20 mg L-1 and 6.0×10-3 mg L-1 for hydrochlorothiazide. Subsequently, to avoid tedious separation procedure and improve the accuracy and precision for determination for the analytes, various chemometrics approaches, such as PARAFAC, NPLS, PCR, PLS and RBF-ANN, without and with taking first-derivative, were introduced to model the kinetic data of the synthetic mixtures. The method was successfully applied for the assay of the studied drug in mass-reducing tonic samples. The results obtained were in good agreement with those obtained with the reference HPLC method.