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研究生:林鴻明
研究生(外文):Hong-Ming Lin
論文名稱:ketamine及其代謝物再尿液中與大腦中之偵測
論文名稱(外文):The determination of ketamine and its metabolites in urine and brain
指導教授:梁偉明梁偉明引用關係
學位類別:碩士
校院名稱:靜宜大學
系所名稱:應用化學研究所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2005/06/
畢業學年度:93
語文別:中文
論文頁數:66
中文關鍵詞:K他命微透析技術
外文關鍵詞:microdialysisketamine
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K它命是一種普遍的麻醉劑,最早被使用於獸醫與小兒科上。此
藥物接著廣氾的被濫用在搖頭舞廳裡,濫用者的增加促使我們必須發
展出一種方法能更容易的偵測出尿液中K它命及其代謝物。在K它命
測試之前,必須先評估K它命及它的兩個主要代謝產物NK和DK在
實際使用藥物者之尿液中的濃度檢測的儀器與方法。
K它命在藥物動力學上的資訊非常的少,在此研究上,我們嘗試
解決這些問題,並發展液態層析術 ( LC ) 與液態層析質譜術( LC/MS )
的分析方法。並使用動物模式來完成K它命及其代謝物的藥物動力學
參數和它的趨勢。在醫院裡,三十個志願者接受K它命的注射 ( 10
mg/person,IM ) 並收集其尿液,並使用LC–MS來檢測其代謝物。在
液態層析質譜術研究中,這些分析物在 12.5-200 ng/mL之間的線性範
圍從0.99912到0.999965。對於K它命、NK及DK的偵測極限 ( S/N=3 )
分別為0.93、0.43和2.54 ng/mL。研究並論證所有年齡層 ( 15~24歲,
25~34歲,35歲以上 ) 其尿液中K它命、NK及DK的時間趨勢。在
所有年齡層中尿液中的K它命及其代謝物於 1~24小時之間的趨勢並
沒有差異。然而,在所有尿液樣品中DK於1至24小時的濃度範圍從
1到312 ng/mL。因此,尿液中的DK可以建議選用為K它命濫用者的
標記或標準指標。
Ketamine, an anesthetic agent primarily used in veterinary medicine
and pediatrics, continues to gain in popularity in the drug abuse scene or
“Rave Wave” of dance clubs. This increasing abuse has led us to consider
developing a simple method to determine urinary ketamine and its
metabolites. Before ketamine testing can be implemented as standard
policy, concentrations of ketamine and its two major metabolites,
norketamine and dehydronorketamine, in urine need to be evaluated after
actual drug use. There is very little information regarding the
pharmacokinetics of ketamine. In this study, we attempt to resolve these
issues with the development of liquid chromatography and liquid
chromatography-mass spectrometry (LC–MS) methods.
The pharmacokinetic parameters and profiles of ketamine and its
metabolites were completed in an animal model. The urine concentrations
of ketamine, its metabolites were detected in 30 volunteers received
ketamine (10 mg/person, im ) accomplished with LC-MS in the hospital.
The linearity of these analytes are 0.99912 to 0.999965 ranged between
12.5 - 200 ng/mL. The limits of detection (S / N = 3) for ketamine,
norketamine and dehydronorketamine were 0.93, 0.43 and 2.54 ng / mL,
respectively. The time profiles of urinary ketamine, norketamine and
dehydronorketamine were investigated and demonstrated in all age groups
(15 - 24 yrs, 25 - 34 yrs and 35 yrs and up). There are no differences of
profiles of urinary ketamine and its metabolites among all age groups
within 1 - 24 h. However, dehydronorketamine concentrations ranged from
1 to 312 ng / mL at 1 to 24 h in all urine samples. It is also proposed that
urinary dehydronorketamine can be an alternative marker for the standard
policy in ketamine abuse scene.
目錄 ----------------------------------------------------------------------- Ⅰ
謝誌 ----------------------------------------------------------------------- Ⅴ
中文摘要 ------------------------------------------------------------------- Ⅵ
英文摘要 ------------------------------------------------------------------- Ⅷ
圖目錄 --------------------------------------------------------------------- Ⅹ
表目錄 ------------------------------------------------------------------- ⅩⅡ
英文縮寫 ----------------------------------------------------------------- ⅩⅢ
第一章 緒論 ----------------------------------------------------------------- 1
壹、K它命部分 --------------------------------------------------------------- 1
一、K它命之簡介 ------------------------------------------------------------- 1
二、K它命之毒性 --------------------------------------------------------- 2
三、K它命之濫用與管制 ------------------------------------------------ 4
四、K它命之藥理作用 --------------------------------------------------- 5
五、K它命之研究 --------------------------------------------------------- 7
貳、質譜儀部分 -------------------------------------------------------------- 8
一、質譜儀簡介 ------------------------------------------------------------ 8
二、離子阱質量分析器 --------------------------------------------------- 8
三、電灑游離法 ----------------------------------------------------------- 11
、微透析部分 ------------------------------------------------------------- 14
一、微透析技術 ----------------------------------------------------------- 14
二、微透析探針之介紹 -------------------------------------------------- 15
三、微透析探針的回復率 ----------------------------------------------- 17
四、微透析技術之應用 -------------------------------------------------- 21
肆、藥物動力學部分 -------------------------------------------------------- 23
一、藥物動力學定義 ----------------------------------------------------- 23
二、藥物的吸收 ----------------------------------------------------------- 23
三、藥物的分佈 ----------------------------------------------------------- 24
四、藥物的代謝 ----------------------------------------------------------- 25
五、藥物的排泄 ----------------------------------------------------------- 26
第二章 K它命及其代謝物之偵測 ------------------------------------------ 28
Part Ⅰ: K它命及其代謝物在尿液中之偵測 ------------------------- 28
2 – 1 – 1 實驗目的 ------------------------------------------------------- 28
2 – 1 – 2 實驗部分 --------------------------------------------------- 29
一、儀器 ----------------------------------------------------------------- 29
二、藥品與試劑 -------------------------------------------------------- 30
三、藥品配製 ----------------------------------------------------------- 31
四、尿液樣品之採集與處理 ------------------------------------------ 33
2 – 1 – 3 結果與討論 ---------------------------------------------------- 34
一、微管層析分離部份 ----------------------------------------------- 34
二、層析質譜圖部份 -------------------------------------------------- 36
三、尿液樣品部份 ----------------------------------------------------- 44
Part Ⅱ: K它命及其代謝物在腦中之偵測 ------------------------------- 51
2 – 2 – 1 實驗目的 ------------------------------------------------------- 51
2 – 2 – 2 實驗部份 ------------------------------------------------------- 51
一、裝置 ----------------------------------------------------------------- 51
二、動物實驗K它命之配製 ----------------------------------------- 51
三、動物實驗之過程 -------------------------------------------------- 52
2 – 2 – 3 結果與討論 ---------------------------------------------------- 55
第三章、結論 --------------------------------------------------------------- 60
第四章、參考資料 ---------------------------------------------------------- 62
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