博士 / 高雄醫學大學 / 藥學研究所 / 98 / The theme of this study is to develop a simple, rapid and high sensitive analytical method for the determination of therapeutic agents. The main works included using MEKC method for the trace analysis of anti-Alzheimer’s disease and anti-Parkinson’s disease agents with low plasma concentrations; or using CZE method for the simultaneous determination of insulin and insulin aspart, which were different in single amino acid. The results are summarized as follow:
I. Trace Analysis of Anti-Alzheimer’s Disease and Anti-Parkinson’s Disease agents by capillary electrophoresis
The works of this study included the development of a CE method with on-line sample stacking to achieve trace analysis of acetylcholine esterase inhibitor (AChEI) agent – donepezil in plasma; and using chemical derivatization combined with CE method to analysis N-methyl D-aspartate (NMDA) receptor antagonist – memantine and its structurally similar compound – amantadine in human plasma. The developed methods were applied in clinical as the reference for physicians to evaluate the therapeutic dosage of patients.
1. Trace analysis of acetylcholine esterase inhibitor (AChEI) – donepezil by capillary electrophoresis
In this work, liquid-liquid extraction (LLE) was used as the pretreatment method to extract donepezil from plasma to organic layer, which was dried and the residue was reconstructed. CE coupled with field amplified sample stacking (FASS) was used to perform on-sample stacking and analysis. The method was applied for monitoring plasma concentration of donepezil in Alzheimer’s disease patients; and evaluates the pharmacokinetic data of a health volunteer.
2. Simultaneous determination of memantine and amantadine in human plasma by capillary electrophoresis coupled with chemical derivatization
A CE method combined with derivatization was developed for the simultaneous determination of memantine and amantadine. The plasma sample was pretreated with LLE, the organic layer was dried and reconstructed with borate buffer to perform chemical derivatization with the labeling reagent – CFSE. The derivatized products were efficiently separated by a MEKC method with non-ionic surfactant Brij-35®. The developed method was applied for the monitoring plasma concentration of memantine and amantadine in Alzheimer’s disease and Parkinson’s disease patients.
II. Simultaneous determination of insulin and insulin aspart by capillary electrophoresis
The main work of this study is to develop a simple capillary zone electrophoresis for the simultaneous determination of insulin and insulin aspart. The structures of regular insulin and insulin aspart are very similar, the amino acid on B28 position was replaced from proline to aspartic acid to form insulin aspart. The BGE used in the study was 80 mM phosphate buffer (pH 6.5), and different parameters were discussed including the concentration and pH value of buffer to optimize the separation condition. The developed method was applied for the analysis of pharmaceutical formulation.
| Identifer | oai:union.ndltd.org:TW/098KMC05551004 |
| Date | January 2010 |
| Creators | Hsin-Hua Yeh, 葉欣樺 |
| Contributors | Su-Hwei Chen, 陳素惠 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 169 |
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