Analysis Of Drugs In Human Body Fluids Samples Using Three Dimensional Fluorescence Coupled With Multi- Way Calibration Methods

In the field of modern analytical chemistry, chemometrics is an important analytical tool for complex chemical system. Second-order calibration method based on three-way data analysis is a hot research area in the theoretical system of chemometrics. It can easily quantify the component(s) of interest even in the presence of the unknown interferences in complex systems. Besides, when the analytes of interest have more heavy matrix effect from complex background, second-order calibration has also some deficiencies. Third-order calibration can extract more useful chemical information from complex system than second-order calibration. In this thesis, second-order calibration and third-order calibration methodologies coupled with fluorescence spectroscopy technology have been tried to the determination of the concentrations of pharmaceutical compounds in human plasma which have been included as follows:1 A new and effective approach was developed for the quantitative analysis of oxaprozin in human urine samples by the incorporation of excitation- emission matrix fluorescence (EEM) and second-order calibration methodologies based on self- weighted alternating trilinear decomposition (SWATLD) and alternating normalization- weighted error (ANWE) algorithms, respectively. With the application of a second-order advantage, excitation spectral profiles and emission spectral profiles of oxaprozin were effectively resolved even in the presence of urine background and other homogeneous drugs such as nabumetone or naproxen. The average recoveries of oxaprozin in urine samples and the precision of test results are satisfactory. The results showed that both algorithms were accurate and reliable. The method is simple,without previous separation procedure.2 Micellar enhancing fluorimetry combining with second-order calibration strategies based on both PARAFAC and SWANRF algorithms was employed to simultaneously determine two components,domperidone and metoclopramide, in plasma complex system. The method light a new avenue to simple experimentation using"mathematical separation"as a replacement of"physical or chemical separation"of uncalibrated background or interferents. Domperidone and metoclopramide are commonly used for gastric motility in clinical medicine. Using both drugs for treatmenting vomiting has achieved a better therapeutic effect. However, because the two drugs are affordable and widely used, the reported adverse reactions are increasing. Metoclopramide half-life is short, the individual differences in pharmacokinetic characteristics is large, and long-term or high doses likely to cause severe extrapyramidal reactions. Hence, it is important to determine the concentration of these compounds for clinical medicine. This research has obtined the spectral resolution, the precise concentrations of domperidone and metoclopramide in human plasma samples even in the presence of unknown interferences.3 Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) developed for the treatment of rheumatoid arthritis and osteoarthritis. Meloxicam shows no fluorescence, but it can be transformed into a highly fluorescent derivative through oxidation reaction with H2SO4. An effective excitation-emission fluorescence method was proposed to determine meloxicam in human urine samples with the aid of second-order calibration methods based on parallel factor analysis (PARAFAC) algorithms and alternating normalization-weighted error (ANWE) algorithms, respectively. The results indicated that non-fluorescence medicine was been indirectly quantified analysis in person urine samples.4 Nabumetone is an oral nonsteroidal anti-in?amatory drug (NSAID) of the acetic acid chemical class and also a prodrug that requires conversion to an active metabolite 6-methoxy-2-naphthylacetic acid for its anti-in?ammatory, analgesic, and antipyretic activity. Because 6-MNA and the blood plasma has the matrix effect,the used second-order calibration methods showed the ineffectiveness in these conditions. Third-order calibration can extract more useful chemical information from complex system than second-order calibration. Thus, a four-way data array was constructed based on the alteration of fluorescence quantum yield by changing the quantity of quencher plasma. Using third-order calibration methods conducted a preliminary research on the determination of 6-MNA in human blood samples.