Second-order Calibration Methods Applied To Determination Of Antitumor Drugs In Complex Systems

Analytical chemistry is a science of chemical measurements, and chemometrics is a new branch of chemistry. First of all, the definition and development of analytical chemistry are described in the introduction part of this thesis, then it is described that the history and development of chemometrics. In addition, its research advance is illustrated. Multivariate resolution and calibration in chemometrics, especially second-order calibration are reviewed, which includes the development of the trilinear component model and its trilinear decomposition algorithms. Then the development of analysis in drugs was given briefly, especially the analysis of vitro drug substance. Based on the above, determination of antitumor drugs in complex systems of human fluids,such as human plasma and urine, have been studied by using second-order resolution and calibration methods combining with excitation-emission matrix fluorescence. The problem of serious spectra overlapping has been successfully solved by utilizing the above method. The method can be used to determine the antitumor drugs in complex systems in the presence of unknown interferences.In Chapter 2, a novel method was proposed for rapid determination of Daunomycin Hydrochloride (DM) in plasma and urine by combining the excitation-emission fluorescence spectra with the second-order calibration based on the alternating trilinear decomposition (ATLD) algorithm. The method didn't need the separate pretreatment procedure such as extraction and the satisfactory results were shown that the proposed method could solve the problem of serious fluorescence spectral overlapping of the sought-for analyte (DM) and plasma or urine interferent(s), and it can be applied to rapid determination of DM even in the presence of unknown interferent(s).Paclitaxel is a novel antitumer agent derived from the bark of one particular type of yew tree Taxus brevifola. Chapter 3 describes a rapid, simple and novel method for determination of paclitaxel with plasma background. The new spectrofluorimetric method is based on excitation-emission matrix (EEM) combining with second-order calibration which has second-order advantage that calibration in the presence of unknown interferents can be performed to provide satisfactory concentration estimates. In this paper, ATLD, parallel factor analysis (PARAFAC) and alternating penalty trilinear decomposition (APTLD) algorithms were proposed as three strategies for determination of paclitaxel in plasma. Though paclitaxel and plasma possessed strongly overlapped fluorescence spectra, that three algorithms could solve the problem of serious fluorescence spectral overlapping of the sought-for analytes even in the presence of uncalibrated interferents. The experimental results showed that three algorithms are good alternatives applied to the quantitative determination of paclitaxel with human plasma interference.In Chapter 4, a novel and rapid method was proposed for rapid determination of resveratrol in plasma and urine by combining the excitation-emission fluorescence spectra with the second-order calibration based on PARAFAC algorithm. It was shown that the proposed method could solve the problem of serious fluorescence spectral overlapping of the sought-for analyte (resveratrol) and plasma or urine interferent(s) , and it can be applied to rapid determination of resveratrol even in the presence of unknown interferent(s).Camptothecin and its ramification of hydroxyamptothecin have good antitumor character, they are two of the most important topoisomeraseâ… (Topoâ… ) inhibitors. Hydroxyamptothecin was developed by Chinese researchers, and it has a broad antitumor effect. It is usually used in therapy of afternoon liver cancer, stomach and intestine cancer, and the curative effect is positive. In Chapter 5, it was tried to use three-way excitation-emission matrix fluorescence combining chemometrics second-order calibration algorithms, including ATLD, alternating fitting residue (AFR), self-weighted alternating trilinear decomposition (SWATLD), determined hydroxyamptothecin with urine background interferent.