Development of high sensitive methods for determination of acetylcholinesterase inhibitors, antipsychotic drugs and a biomarker for Alzheimer’s disease by capillary electrophoresis / 發展高感度毛細管電泳分析法對於血液檢體中乙醯膽鹼酶抑制劑及抗精神病藥物之同時分析及臨床阿茲海默症生物指標之研究

博士 / 高雄醫學大學 / 藥學研究所 / 102 / Alzheimer’s disease (AD) is a degenerative disease and the most common cause of dementia in the elderly. However, the disease is difficult to diagnosis in the early stage and the efficacy of current treatments is very limited. Therefore, accurate diagnosis and control of pharmaceutical treatment are essential.
It has been proved that acetylcholinesterase inhibitors (AChEIs) therapy offers symptomatic benefits - cognitive, functional and behavioral, such as donepezil and rivastigmine. Otherwise, one of atypical or conventional antipsychotic drugs, such as aripiprazole, clozapine, olanzapine, quetiapine, risperidone, trazodone, ziprasidone, etc., is co-administered with AChEIs for improving the AD patients with behavioral and psychological symptoms of dementia (BPSD). Pharmacotherapies may improve the symptoms of AD, but there is no cure for AD. So, the relationships between the concentrations of AD medication and the biomarker (haptoglobin), and therapeutic efficacy are useful for early diagnosis of AD and for monitoring its course.
A simple and sensitive capillary electrophoresis (CE) with UV detection was developed and validated for the simultaneous determination of AChEIs with antipsychotic drugs in human plasma. A sample pretreatment by liquid–liquid extraction and subsequent quantification by CE with field-amplified sample injection (FASI) was used. And immunoaffinity extraction was coupled with CE to determine haptoblobin concentrations indirectly by using magnetic nanobeads (MBs) as a support and laser-induced fluorescence detection.
The first proposed method was applied for concentrations monitoring of AChEIs and antipsychotic drugs in AD with BPSD. The method may also be used to investigate the relationship between concentration of AChEIs and antipsychotic drugs in plasma and the therapeutic effectiveness in AD with BPSD. Besides, the second proposed method was validated for quantifying haptoglobin in AD with BPSD. And the method can also be used to investigate the relationship between haptoglobin concentration in human plasma and the course of AD with BPSD.

Identiferoai:union.ndltd.org:TW/102KMC05551041
Date January 2014
CreatorsYi-Rou Wang, 王易柔
ContributorsSu-Hwei Chen, 陳素惠
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format171

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