利用微透析和液相層析來測定大鼠血液中的Galantamine

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標題:	利用微透析和液相層析來測定大鼠血液中的Galantamine Determination of galantamine in rat blood by microdialysis and liquid chromatography
作者:	麥宜傑
貢獻者:	林維炤嘉南藥理科技大學：藥物科技研究所
關鍵字:	微透析 Galantamine Microdialysis Galantamine
日期:	2010
上傳時間:	2010-12-30 15:34:04 (UTC+8)
摘要:	Galantamine 是一種目前廣泛應用於治療阿茲海默症的化合物，是一種乙醯膽鹼酵素抑制劑。目前有關galantamine的代謝研究均需要經過複雜的樣品前處理步驟，開發簡單的樣品前處理分析方法為一重要的課題。本研究應用微透析系統與高效率液相層析儀測定老鼠血液中的galantamine。將老鼠血液中的galantamine以微透析方式直接收集後，直接注入高壓液相層析進行分析。除了不需要複雜的前處理過程之外，給藥後到透析完畢都是活體狀態，更能得到真實樣品與數據。本研究分成三個部分進行。首先建立層析分離條件。以氰甲烷與磷酸水緩衝溶液為移動相，以螢光偵測器作為偵測器。激發波長為280nm與放射光波長為310nm，使用管柱為Discovery HS F5。其次探討微透析條件。研究中評估兩種不同品牌之探針，在同樣的濃度下做回收率的比較，透析液流速為1μL/min，在體外(in vitro)與體內(in vivo)下較佳的探針所測得的回收率約50%。最後進行活體測試，大鼠以濃度10mg/kg靜脈給藥後，以微透析系統進行血液取樣每30分鐘取樣一次，由圖譜顯示得知，在30分鐘取樣點即得最大濃度。活體試驗的結果說明以微透析方式進行血液中測定藥物galantamine是可行的。 Galantamine is a chemical widwly used for the treatment of mild to moderate Alzheimer’s disease.It is a cholinesterase inhibitor.The present studies for the metabolism of galantamine in iological fluid need complicated pretreatment procedure.The development of a simple analytical method for galantamine is an important issue. This investigation uses the microdialysis system and high performance liquid chromatography (HPLC) to determinate galantamine in rat blood. The galantamine in rat blood was directly collected by microdialysis without any sample pretreatment then quantification by HPLC. This analytical method can be applied on the in vivo evaluation of galantamine metabolism in living organism. The development of this study is divided in to three parts. First is to find optimum HPLC separation condition. Galantamine and its four metabolites can be well separated by using acetonitrile and waters containing phosphoric acid as mobile phase. A fluorescence detector is used for monitoring these compounds. The excitation wavelength is 280 nm and emission wavelength is 310 nm. The separation column is Discovery HS F5..Second is to develop the microdialysis condition. Two different brands of probes were used to evaluate the recoveries of galantamine at sample concentration of galantamine in blood. The recovery is approximately 50% at 1 μL/min perfuse flow. The last step is to evaluate this analytical method on in vivo test of rat. The subject was given 10mg/kg of galantamine into a vein. The concentration of galantamine in blood vessel was directly sampled by microdialysis at the interval of 30 min. the maximum concentration was happened at first 30 minute. These result showed this analytical method can be applied on the in vivo galantamine metabolism study.
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顯示於類別:	[藥學系(所)] 博碩士論文

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