Structual Analysis Of Second-order Calibration Algorithms And Quantitative Analysis Of Pharmaceuticals In Complex Dynamical Systems Using Multi-way Calibration Methodologies

Chemometrics is an interdisciplinary field, lying between the more established fields of chemistry, mathematics, statistics and computer sciences. The combination of instrument analysis and chemometric methodologies provides a new avenue to extract the information of analytes in complex systems. With the development of high-order analytical instrumentation, multi-way data analysis has become an active domain with practical significance. The research work in this thesis focuses on structual analysis of second-order calibration algorithms and quantitative analysis of pharmaceuticals in complex dynamical systems using multi-way calibration methodologies in complex systems.1. Structural analysis of second-order calibration algorithms (Chapter 2):According to comparisons of several second-order calibration algorithms and practical applications, it was found that the analytical results of the self-weighted alternating trilinear decomposition (SWATLD) and the alternating penalty trilinear decomposition (APTLD) algorithms were very similar. Hence, we analyzed the objective function of the two algorithms to explore the reasons for this phenomenon in chapter 2.The mathematical expressions of the objective functions were split into corresponding several categories. Then, a set of simulated data was used to investigate the performance of the two algorithms on the whole, and so did those corresponding parts of formula partially. The structural analysis provides some valuable references to the development of new algorithms and improvement of algorithms performance.2. The application of multi-way calibration in complex dynamical systems (Chapter 3 to Chapter 5)Monitoring the dynamical process of chemical reactions and quantitative analysis in complex dynamical systems is an important aspect in chemistry. It is very difficult to achieve this objective using traditional methods, especially for the quantitative analysis in complex system involved of uncalibrated interference. It is convenient to implement the objective using multi-way calibration methodologies with second-order and three-order advantage.Epinephrine and norepinephrine are all catecholamine hormones with weak fluorescence. They could be gradually converted to a highly fluorescent intermediate product by oxidation reaction, and further to non-fluorescent degradation product (o-quinone). Fluorescence spectra were measured at consecutive time points in the case of kinetic-emission determination. Hence, a three-way response data array was created and then analyzed by trilinear decomposition method. In chapter 3, a kinetic fluorometric method was proposed for the quantitative determination of epinephrine in human plasma samples with the aid of second-order calibration methods based on alternating trilinear decomposition (ATLD) and alternating fitting residue (AFR) algorithms. Similarly, in chapter 4, second-order calibration methods based on parallel factor analysis (PARAFAC) and full rank parallel factor analysis (FRA-PARAFAC) algorithms were employed for the quantification of noradrenaline in human plasma. The emission spectra profiles as well as the kinetic evolution profiles of the intermediate were obtained. The concentration predicted results indicated that these second-order calibration algorithms provided for the analysis with a satisfactory prediction capacity.Procaine hydrochloride is a commonly used local anesthetic, which is easily hydrolyzed to p-aminobenzoic acid and diethylamino ethanol. The hydrolysis rate accelerated along with the increase of OH-1 concentration at a certain temperature. In chapter 5, we introduced the fourth dimension (pH dimension) in the design of experiment according to this property. A four-way response data array was constructed by measuring excitation-emission matrix fluorescence of different concentrations of procaine hydrochloride in five different pH values. Third-order calibration methods based on quadrilinear PARAFAC and alternating penalty quadrilinear decomposition algorithm (APQLD) were used for quantitative analysis of procaine hydrochloride in human plasma.These works in this thesis provide some new ideas in the research of chemical kinetics in complex systems using multi-way calibration methodologies, and validate the advantage and potential of multi-way calibration in dynamical systems.3. The applications of second-order calibration in pharmaceutical analysis (Chapter 6 to Chapter 7)Generally, there are two most representative types in the practical application of second-order calibration methodologies, which are combinations of second-order correction with excitation emission matrix fluorescence (EEM) or high performance liquid chromatography-diode array detection (HPLC-DAD). The works in chapter 6 and chapter 7 are two examples of pharmaceutical analysis in biological matrix using second-order calibration coupled with two types of data. Fluphenazine hydrochloride is widely used in the treatment of psychotic patients. Taking into account its relatively extensive practicability and possible health effects, it is thus important for quantitative analysis of Fluphenazine hydrochloride in body fluids. It can be transformed into a highly fluorescent derivative through oxidation reaction with KMnO4. In chapter 6, an effective excitation-emission fluorescence method was proposed to determine fluphenazine hydrochloride in presence of chlorprothixene in human urine samples with the aid of second-order calibration methods based on the full rank parallel factor analysis (FRA-PARAFAC) and parallel factor analysis (PARAFAC) algorithms respectively.Levodopa is widely used in the clinical treatment of Parkinson's disease. It is often administered in combination with carbidopa, an inhibitor of the decarboxylase enzyme. Methyldopa is one of the most important impurities in the analysis of levodopa-carbidopa combination formulation. The determination of levodopa and its inhibitors and impurities in biological fluids have an essential role in the diagnostics of diseases related to them. In chapter 7, an HPLC method combined with second-order calibration based on alternating trilinear decomposition (ATLD) algorithm has been developed for the quantitative analysis of levodopa, carbidopa and methyldopa in human plasma samples. Prior to the analysis of the analytes by ATLD algorithm, three regions of chromatograms were selected purposely for each analyte to avoid serious collinearity. Although the spectra of these analytes were similar and interferents coeluted with the analytes studied in biological samples, good recoveries of the analytes could be obtained with HPLC-DAD coupled with second-order calibration based on ATLD algorithm, additional benefits are decreasing times of analysis and less solvent consumption.