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系統識別號 U0007-1704200714542067
論文名稱(中文) 服用複方甘草合劑於尿液中嗎啡及可待因含量分析
論文名稱(英文) Urinary Excretion of Morphine and Codeine Following the Administration of Brown Mixture
校院名稱 臺北醫學大學
系所名稱(中) 藥學研究所
系所名稱(英) Graduate Institute of Pharmacy
學年度 93
學期 2
出版年 94
研究生(中文) 劉秀娟
研究生(英文) Hsiu-Chuan Liu
學號 M301092006
學位類別 碩士
語文別 中文
口試日期
論文頁數 138頁
口試委員 指導教授-何秀娥
中文關鍵字 複方甘草合劑  可待因  嗎啡 
英文關鍵字 Brown Mixture  codeine  morphine 
學科別分類
中文摘要 如同罌粟子因素(poppy-seed defense)在美國所引起之爭議,在臺灣當尿液檢測結果呈現鴉片類陽性反應時,受檢者常辯稱是因為服用複方甘草合劑(Brown mixture)而導致尿液中morphine和codeine成分的出現。複方甘草合劑乃一常用之藥品,在藥品處方中含有鴉片粉、鴉片酊或鴉片樟腦酊成分,而由於海洛因的使用為持續存在的嚴重社會問題,所以對於服用複方甘草合劑所導致的尿液檢驗結果必須與之作一明確區隔。 本篇論文分析方法為將檢品經水解、萃取、衍生,最後以氣相層析質譜儀(GC/MS)檢測。所用trimethylsilyl (TMS)衍生之codeine、morphine和nalorphine (IS)選擇監測之離子分別為m/z 371、356、343;429、414、401和455、440、414,上列化合物之第一個離子用於定量。結果顯示此分析方法對於複方甘草合劑製劑及尿液中morphine和codeine濃度的定量具有相當好的靈敏度與再現性;在檢量線濃度50-1500 ng/ml的範圍之內呈現良好的線性關係,其回收率可達80%。精密度評估同日內及異日間確效的偏差各在0.99~5.69%及0.81~3.58%之間;準確度評估同日內及異日間確效的偏差各在-3.96~2.52%及-5.33~7.84%之間,顯示此分析條件適合用於分析複方甘草合劑製劑及尿液中微量的morphine和codeine。 蒐集八種不同廠牌複方甘草合劑(含錠劑和溶液劑)及收集病患尿液檢體分析其內morphine和codeine含量,實驗結果顯示複方甘草合劑不同廠牌錠劑間其嗎啡和可待因含量相等,而在二種溶液劑間則有明顯差異。在正常治療情況下,不管是服用複方甘草合劑錠劑或溶液劑,尿液中morphine濃度通常不會大於4000 ng/ml。當尿液中嗎啡濃度大於300 ng/ml時,其嗎啡/可待因比值可歸納為以下二種情況:(1)小於3.0為複方甘草合劑溶液劑使用者;(2)大於3.0為複方甘草合劑錠劑或海洛因使用者。綜上所述,顯示(1)服用複方甘草合劑不易導致尿液中嗎啡濃度高於4000 ng/ml;(2)無法利用尿液中嗎啡/可待因比值作為分辨複方甘草合劑錠劑和海洛因使用者之指標。
英文摘要 Parallel to the "poppy-seed defense" strategy commonly reported in the United States, donors of urine samples tested positive for opiates in Taiwan often claimed the consumption of Brown Mixture (BM) as the source of the observed morphine and codeine. Since BM contains opium powder, opium tincture, or camphorated opium tincture and is a popular remedy, while heroin use is considered a serious criminal act, the claim of BM use has to be adequately addressed. The analytical procedure included hydrolysis, trimethylsilylation and GC-MS analysis, monitoring the following ions designated for TMS-derivatized codeine, morphine, and nalorphine (internal standard):m/z 371, 356, 343;429, 414, 401;455, 440, 414, respectively. The first ion listed for each compound was used for quantitation. A linear relationship was found in the range from 50 to 1500 ng/ml with absolute recovery about 80%. Precision for intraday and interday is from 0.99% to 5.69% and from 0.81% to 3.58%, respectively. Accuracy for intraday and interday is from –3.96% to 2.52% and from –5.33% to 7.84%, respectively. In this study, BM from eight different manufacturers (tablets and solutions) and urine samples from patients were analyzed for their morphine and codeine contents. The contents of morphine and codeine in tablets are very consistent, but vary considerably in the BM solutions. Morphine concentrations found in urine specimens collected from volunteer patients ingesting BM tablets (or solutions) are always <4000 ng/mL. The following morphine/codeine concentration ratios ([M]/[C]) were observed for urine specimens with morphine concentration ? 300 ng/mL:(a) <3.0 for patients ingesting BM solution; (b) >3.0 (mostly >5.0) for patients ingesting BM tablets and alleged heroin users. It appears that (a) BM ingestion (tablet or solution) is unlikely to result in morphine concentration >4000 ng/mL; and (b) [M]/[C] ratio may not be an effective parameter to differentiate heroin use from BM tablet ingestion.
論文目次 目 錄 i 附表目錄 iii 附圖目錄 v 中文摘要 x 英文摘要 xii 研究動機 xiii 第 一 章 Morphine和Codeine之氣相層析質譜(GC/MS)分析方法之建立 1 壹、緒論 2 第一節 海洛因、嗎啡和可待因 3 第二節 氣相層析質譜分析法 8 貳、實驗材料與方法 14 第一節 實驗材料 14 第二節 實驗儀器 15 第三節 實驗方法 15 參、結果與討論 20 第一節 衍生劑評估 20 第二節 GC/MS內標準品之評估 24 第三節 GC/MS昇溫程式的建立 36 第四節 morphine與codeine定量分析方法 41 肆、參考文獻 43 第 二 章 複方甘草合劑之藥物分析 45 壹、緒論 46 第一節 複方甘草合劑介紹 47 第二節 複方甘草合劑定量方法 51 貳、實驗材料與方法 53 第一節 實驗材料 53 第二節 實驗儀器 54 第三節 實驗方法 55 參、結果與討論 60 第一節 複方甘草合劑中morphine與codeine的含量分析 60 第二節 複方甘草合劑製劑中morphine與codeine含量比例 68 肆、參考文獻 69 第 三 章 複方甘草合劑之尿液分析 70 壹、緒論 71 第一節 國內濫用藥物尿液檢驗概況 72 第二節 尿液檢驗結果的解釋與探討 75 貳、實驗材料與方法 79 第一節 實驗材料 79 第二節 實驗儀器 80 第三節 實驗方法 80 參、結果與討論 88 第一節 尿液中嗎啡結合型的水解效率 89 第二節 尿液中嗎啡與可待因的萃取方法評估 90 第三節 分析方法的確效 91 第四節 偵測極限與定量極限 97 第五節 藥物動力學試驗 99 第六節 海洛因的尿液分析 131 肆、參考文獻 135 結 論 137
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