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研究生:顏祥
研究生(外文):Hsian Yen
論文名稱:利用電噴灑串聯質譜同時偵測麻黃鹼和假麻黃鹼與其他感冒藥
論文名稱(外文):Simultaneous determination of ephedrine / pseudoephedrine and other cold medicines in urine samples by Electrospray ionization-tandem mass spectrometry
指導教授:賴滄海賴滄海引用關係
指導教授(外文):Ahai chang Lua
學位類別:碩士
校院名稱:慈濟大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
畢業學年度:97
語文別:中文
論文頁數:126
中文關鍵詞:麻黃電噴灑串聯質譜儀
外文關鍵詞:ephedrinepseudoephedrineESI-MS/MS
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中文摘要
假麻黃鹼是麻黃鹼的非鏡像異構物,是天然的生物鹼,協同其他的藥物,廣泛的應用於治療一般性感冒與呼吸道過敏,如同其他中樞神經興奮劑一樣,假麻黃鹼與麻黃鹼也有藥物濫用情形產生。然而,在製造非法的甲基安非他命時,假麻黃鹼及麻黃鹼為主要的原料。
我們所開發的方法是用電噴灑液相質譜儀與電噴灑液相層析質譜儀的方法來分析尿液檢體中十二種包含假麻黃鹼與麻黃鹼的感冒藥,以500 ng / mL 作為判定陽性的閾值,在假麻黃 鹼或麻黃鹼呈現陽性的檢體中,在調整pH值後以液相萃取,並設計兩階段的分析方法,第一階段初步篩檢,以直接注射液相質譜儀分析。液相中,所用的移動相為二次水含0.1%甲酸(50%)與以及甲醇含0.1%甲酸(50%),不經層析管柱,在最佳的流速為0.2 mL / min下,直接液相串聯質譜儀分析,二次質譜設定撞擊能量介於6-24 eV,以選擇反應監測模式分析,第二階段確認檢驗以 C18層析管柱配合液相層析程式來分析。這個方法主要應用在確認及定量檢體中麻黃鹼/假麻黃鹼及其他感冒藥中的藥物,以判定是否服用感冒藥或是非法藥物。感冒藥則包含止痛藥、抗組織胺類劑、解鼻充血劑以及止咳劑。
Abstract

L-(+)-Pseudoephedrine (PEP) is the (S,S) diastereoisomer of ephedrine (EP), it is a naturally occurring alkaloid. Pseudoephedrine and ephedrine are widely used in combination with other drugs for the clinical treatment of common cold, respiratory allergies. Pseudoephedrine and ephedrine , like other stimulants has been abused , are used as key ingredient for the production of the illicit drug (D)-methamphetamine.
The objective of this study is to develop a simple ESI-MS/MS and LC-ESI-MS/MS methods for the screening and confirmation of 12 active ingredients commonly found in cold medicine, including pseudoephedrine and ephedrine in urine samples. The study is used to screen urines for the presence of pseudoephedrine / ephedrine at a cutoff concentration of 500 ng / mL. The urine samples were extracted by liquid /liquid extraction (LLE) after adjustment of its pH. For the screening procedure, extracts were injected directly into ESI-MS/MS system. The mobile phase was 50% water containing 0.1% formic acid and 50% methanol containing 0.1% formic acid .The analysis was performed at a flow rate of 0.2 mL / min and monitored with selected reaction monitoring (SRM) at an selected collision energy of 6 to 24 e V . For confirmation procedure, the separation of these cold medicines was achieved within 13 min on C18 column using LC gradient program. The analysis was performed at a flow rate of 0.32 mL / min and monitored with selected reaction monitoring (SRM) .The method was applied to determine whether pseudoephedrine and ephedrine were abused alone or co-administered with other ingredient in cold formulations. The cold medicines contain other ingredient such as analgesic, antihistamine, decongestant and antitussive.
目錄
中文摘要..................................................................................................I
英文摘要..................................................................................................II
壹、 緒論
1-1背景介紹 ..................................................................................1
1-2認識綜合感冒藥之主要成份...................................................2
1-3 藥物之檢測..............................................................................8
1-4電噴灑串聯質譜儀(ESI-MS/MS)之介紹............................8
1-5相關文獻回顧.........................................................................12
1-6研究動機與目的......................................................................13
貳、 實驗方法
2-1藥物與化學溶劑....................................................................14
2-2 氣相層析質譜儀之資料庫比對.............................................16
2-3衍生步驟..................................................................................16
2-4檢體來源...............................................................................16
2-5 萃取方法選擇.........................................................................17
2-6儀器設備與參數設定 ............................................................18
2-7校正曲線之測定-初步篩檢 ............................... .................. 24
2-8 校正曲線之測定-確認檢驗...................................................24
2-9 準確度 與精密度的評估(初步篩檢).................................24
2-10 準確度與精密度的評估(確認檢驗)..................................25
2-11 回收率評估.......................................................................... 25
2-12 實際樣品之檢測.................................................................. 26
�H、結果與討論
3-1未檢驗之其他感冒藥成份......................................................27
3-2校正曲線之評估(初步篩檢).............................................27
3-3校正曲線之評估(確認檢驗)..................................................27
3-4準確度與精密度的評估(初步篩檢).....................................28
3-5準確度與精密度的評估(確認檢驗).....................................28
3-6初步篩檢 ................................................................................29
3-7確認檢驗 ................................................................................29
3-8本研究方法與其他方法比較..................................................30
肆、結論 .................................................................................31
伍、參考資料 .......................................................................32
陸、附件資料 ......................................................................121
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