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研究生:陳俊豫
研究生(外文):Chun-Yu
論文名稱:毛髮中酸性化合物:γ-hydroxybutyrate 之質譜研究與探討
論文名稱(外文):Determination of acidic compound : γ-hydroxybutyrate in hair by Gas chromatography/mass spectrometry
指導教授:張耀仁張耀仁引用關係
指導教授(外文):Yan-Zin Chang
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:醫學分子毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:70
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GHB 學名 gamma-Hydroxybutyric acid,是一種含四碳之有機酸,可由人體自行產生,為中樞神經系統中重要的抑制性傳導物質;也可由人工方式合成,醫療上常用以治療失眠、戒酒、戒毒及罕見疾病猝睡症( Narcolepsy )。但由於施用後會產生欣快感,因此 GHB 亦遭濫用成為新興之俱樂部藥丸。GHB 在國外已濫用多年,因此於尿液、血液等其他生物基質之檢測方法已相當成熟,但於毛髮中之分析研究仍相當有限。本研究中,我們發現經由超音波震盪處理,可提高 Phosphate buffer 對毛髮中 GHB 之萃取效率,結合氣相層析質譜( GC-EI/MS )進行分析研究,其方法之回收率可達 90% 以上,方法偵測極限為 25 pg/mg,最低定量極限為 100 pg/mg。
方法應用上,我們發現以市售染髮霜漂淡之毛髮檢體中,其 GHB 含量下降之幅度約為其他濫用藥物 1.5 - 3 倍,包括:甲基安非他命、安非他命、K 他命、Norketamine、6-乙醯嗎啡及嗎啡,顯示 GHB 可做為一靈敏之生物性內標,有助於避免檢體經刻意漂洗後使藥檢呈偽陰性之風險。另外我們模擬無 GHB 之毛髮浸泡大麻酸標準品,結果發現大麻酸進入量多了約 1.6 倍,顯示大麻酸與 GHB 在毛髮中有部份重疊之結合位,而使大麻酸相較其他藥物在毛髮中可保存之濃度低了許多。

GHB, gamma-Hydroxybutyric acid, is an organic acid naturally produced by human body. It is an important inhibitory neurotransmitter in central nervous system. Besides, when artificially synthesized, GHB is used frequently in the treatment of insomnia, alcoholism, substance addiction, and narcolepsy. However, due to its cause of euphoria after consumption, GHB now becomes one of the abused substances. Abuse of GHB has been an issue for years in other countries. Thus, methods are well-developed in detecting this chemical from biological tissues or fluid such as urine and blood. Even so, the researches conducted in body hair analysis are still limited. In this study, phosphate buffer was applied to extract GHB fromhair, the extraction efficiency of GHB from hair was increased under ultrasonic bath. The sample was dried, derivatized and finally analyzed by the GC-EI/MS. The recovery of GHB in this method could reach 90% and the detection limit was 25 pg/mg.
This study shows the GHB amount in the hair decrease 1.5 – 3 times
more than other abused substances in real sample after treated by the
commercial available hair highlighter. The substances(abused) include
methamphetamine, amphetamine, ketamine, norketamine, 6-acetylmorphine,and morphine. Therefore, it is important to establish an effective methodology to determine the GHB concentration to avoid the false negative. In this study, the hair without GHB was soaked into the THC-COOH
standard solution. The results show the THC-COOH concentration was 1.6
times higher than that with GHB. The possible reason is both the GHB and
THC-COOH have the same binding site. However, in the normal condition, the intrinsic GHB occupies most binding sites, so THC-COOH cannot be
kept in the hair easily.

中文摘要...................................................................................................I
英文摘要................................................................................................. II
總目錄....................................................................................................IV
圖目錄....................................................................................................VI
表目錄.................................................................................................. VII
第一章 前言............................................................................................ 1
1-1 GHB 之介紹及相關文獻回顧............................................................... 1
1-2 內生性 GHB 之代謝機制.................................................................... 4
1-3 GHB 之藥理作用及動力學.......................................................... ........5
1-4 GHB 之 GC/MS 分析方法回顧............................................................ 8
1-5 濫用藥物之檢測.............................................................................. 10
1-6 毛髮之生理與結構...................................................................... .....12
1-7 氣相層析質譜儀......................................................................... .....16
1-8 研究動機.........................................................................................23
第二章 材料與方法............................................................................. ....25
2-1 藥品與試劑.................................................................................... 25
2-2 工作溶液之配製......................................................................... .....26
2-3 儀器設備及分析條件. .......................................................................28
2-4 實驗方法........................................................................................ 30
第三章 毛髮中 GHB 檢測方法之建立......................................................... 37
3-1 GHB 之 GC-EI/MS 偵測模式建立........................................... ...........37
3-2 毛髮中 GHB 萃取方法之評估與建立................................................... 40
3-3 方法確效性評估.............................................................................. 47
3-4 毛髮中 GHB 樣品之探討....................................................................52
3-5 毛髮中內生性 GHB 對大麻酸結合位之研究探討................. ..................57
第四章 結論與未來展望........................................................................... 65
參考文獻................................................................................................67


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