The Application Of Three-way Fluorescence Coupled With Second-order Calibration Algorithms In Pharmaceutical Analysis System

In the introductory part of this thesis, the background and history of chemometrics and its research advances are illustrated. The second-order calibration in chemometrics was a core field with mighty advantages. It included the development of the trilinear decomposition algorithms as well as the applications of these algorithms to different fields of analytical chemistry, such as in pharmaceutical chemistry, environment, medicine, food and so on. In particular, three-way fluorescence (excitation-emission matrix fluorescence) coupled with second-order calibration has gained important development and applications in pharmaceutical analysis in complex matrix, e.g. plasma or urine. In Chapter 2, a method was proposed for simutaneous determination of ofloxacin (OFL), norfloxacin (NOR) in the presence of enoxacin (ENO) by combining excitation –emission fluorescence with second-order calibration based on alternating trilinear decomposition algorithm. This method was satisfactorily applied to the quantification of OFL and NOR in pharmaceutical preparations. Moreover, this method has also been used for simultaneous direct determination of OFL, NOR and ENO in plasma with satisfactory results. The results showed that this algorithm could solve the problem of serious fluorescence spectral overlapping of the sought-for analytes and determine simultaneously them even in the presence of uncalibrated interferents. An excitation-emission matrix fluorescence (EEMs) method combined with chemometrics methods was also utilized to detect directly procaine hydrochloride in plasma in Chapter 3. Procaine hydrochloride is a local anesthetic drug, which can block the conduction of nerve fibers. So it has narcotism and its doseage must be controlled. The determination of procaine hydrochloride in plasma is of an important meaning. It was showed that these methods are able to handle the occurrence of interference not modeled in the calibration set, which presents "second-order advantage". In Chapter 4, a combination of EEMs with second-order calibration was applied for determination of daunomycin hydrochloride, an antineoplastic drug, in plasma and urine. It has characters of binding of daunomycin to DNA and the inhibition of RNA and DNA synthesis. The determination of daunomycin hydrochloride in plasma or urine has a vitally important meaning. The method was used for direct determination of daunomycin hydrochloride in plasma or urine by combining excitation-emission fluorescence with second-order calibration based on alternating trilinear decomposition algorithm. The satisfactory results can be gained in complex matrix (plasma or urine), which contains some uncalibrated interferences. In Chapter 5, a newly developed method, an alternating normalization-weighted error (ANWE), was utilized to three-way excitation-emission matrix fluorescence data analysis for second-order calibration. A prominent advantage of the method is that the resolved results are very stable with respect to the model dimensionality when the dimensionality chosen is not less than the actual number of components, escaping the dilemma in selection of an actual component number for the model. Moreover, the proposed algorithm can overcome the slow-convergence brought about by random initialization or high multicollinearity to some extent. By treating one real excitation-emission spectral data sets, the results demonstrated that the proposed method performs well as long as the model dimensionality chosen is not less than the actual number of components. This method has been satisfactorily applied to determinate salicylamide and salsalate in presence of naproxen.