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研究生:蘇霖榛
研究生(外文):Lin-Jhen Su
論文名稱:在緊急救護領域裡以大氣游離質譜法快速識別草藥中未標示的活性藥物成分
論文名稱(外文):Rapid Characterization of Undeclared Active Pharmaceutical Ingredients in Herbal Remedies by Ambient Ionization Mass Spectrometry in Emergency Settings
指導教授:謝建台李啟偉李啟偉引用關係
指導教授(外文):Shiea,Jen-TaieLEE CHI-WEI
學位類別:碩士
校院名稱:國立中山大學
系所名稱:醫學科技研究所
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:2022
畢業學年度:110
語文別:中文
論文頁數:80
中文關鍵詞:混充藥物草藥大氣質譜固相微萃取熱脫附電噴灑游離法
外文關鍵詞:Adulteratedherbal preparationsAmbient Ionization Mass Spectrometrysolid phase microextractionThermal Desorption-Electrospray Ionization/Mass Spectrometry
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在草藥製劑中混充藥物成分已經是一項嚴重的公共衛生問題,不只是在台灣,在全球各地都有相關的案例被報導出來。商人在進行這種違法行為的時候通常不會考慮藥物成分在人體中的安全劑量問題,所以導致服用這些草藥製劑的人可能會產生嚴重的急性不良反應,最嚴重的後果就是死亡。所以為了及時拯救這些食入混充藥物者的生命我們必須開發出一套快速且精準的檢測方式來鑑定他們所攝入的藥物。
大氣游離質譜法(AIMS),是一種近十幾年蓬勃發展的質譜檢測技術,它的特點就是所檢測的樣品不需經過繁雜的前處理就可以進行分析,而本實驗使用熱脫附電噴灑游離質譜法(TD-ESI/MS)來檢測摻入各種基質的混充藥物,例如:草藥製劑的粉末、人類的胃液引流液、人類的血清,並對最低偵測極限和重複性等進行探討。
本研究第一部分使用金屬採樣探針進行,實驗結果顯示出TD-ESI/MS對於可以成功的檢測出草藥粉末中的藥物,並且在粉末樣品中最低偵測濃度可以達到0.01ppm。
而第二部分的研究則是檢測摻入生物基質中的藥物並搭配固相微萃取技術(SPME)來檢測人類血清中的藥物,並探討吸附時間、最低偵測極限,由實驗結果顯示出SPME-TD-ESI/MS對於可以成功地檢測出血清中的藥物,並且周轉時間及偵測濃度都可以達到急診救護的應用門檻。
In Taiwan, as well as throughout the world, adulterated western medicine ingredients in herbal preparations have become a major public health problem. Businessmen who engage in such illegal activities are usually unaware of the safe dosage of western medicine ingredients in the human body. As a result, people who take these herbal preparations could suffer severe acute adverse reactions, the most serious of which is death. Therefore, in order to save the lives of these people who ingest mixed drugs in time, we must develop a rapid and accurate detection method to identify the western medicine they ingested.
Ambient Ionization Mass Spectrometry (AIMS) is a mass spectrometry detection technology that has developed vigorously in the past ten years. Its characteristic is that the detected samples can be analyzed without complicated pretreatment. Thermal Desorption-Electrospray Ionization/Mass Spectrometry (TD-ESI/MS) was used to detect drugs mixed with various matrices, such as: herbal preparation powder, human gastric drainage fluid, human serum. The minimum detection limit and repeatability are discussed.
The first part of this study was carried out using a metal sampling probe. The experimental results showed that TD-ESI/MS can successfully detect western medicines in herbal powders, and the lowest detection concentration in powder samples can reach 0.01ppm.
In the second part of this study, detection of drugs incorporated in biological matrices (like human gastric aspirate and human serum) was achieved by using solid phase microextraction (SPME). Parameters like the adsorption time,detection limit, etc. were optimized. The experimental results showed that SPME-TD-ESI/MS can successfully identify drugs in serum, and both the turnaround time and limit of detection can meet the requirements of emergency rescue.
論文審定書 i
誌謝 ii
摘要 iv
Abstract v
目錄 vii
圖目錄 x
表目錄 xii
第一章 緒論 1
1.1 前言 1
1.2電噴灑游離法 (Electrospray Ionization, ESI) 2
1.3 大氣游離質譜法(Ambient Ionization Mass Spectrometry, AIMS) 3
1.3.1直接電噴灑探針(Direct Electrospray Probe, DEP) 3
1.3.2脫附電噴灑游離法 (Desorption Electrospray Ionization, DESI) 4
1.3.3 熱脫附電噴灑游離法 (Thermal Desorption Electrospray Ionization, TD-ESI) 5
1.4 固相微萃取技術 (Solid Phase Microextraction, SPME) 6
1.5 固相微萃取結合大氣游離質譜技術 7
1.5.1 固相微萃取結合直接電噴灑探針質譜法 (Solid Phase Microextraction-Direct Electrospray Probe-Mass Spectrometry) 7
1.5.2 固相微萃取直接結合質譜儀(Direct SPME–MS) 9
1.5.3固相微萃取結合探針電噴灑游離技術(Solid-phase Microextraction- Probe Electrospray Ionization) 10
1.5.4固相微萃取結合大氣游離質譜技術比較 10
1.6 真實案列 11
1.7 研究動機與目的 13
第二章 實驗器材與方法 14
2.1 實驗試劑與藥品、器材 14
2.1.1 試劑 14
2.1.2 藥品 14
2.1.3 生物體液 15
2.1.4 器材與設備 15
2.1.5 藥品與樣品製備 15
2.1.6 待測藥物 17
儀器與參數設定 20
2.2.1 質譜儀檢測模式 20
2.2.2 TD-ESI/MS 22
2.2.3 LC-MS/MS 24
2.3 實驗流程與設計 26
2.3.1 TD-ESI實驗流程 26
2.3.2 SPME-TD-ESI實驗流程 27
第三章 結果與討論 28
3.1 第一部分 : 以TD-ESI/MS快速測定草藥製劑中的未標示藥物 28
3.1.1 建立目標物分析資料庫 28
3.1.2 分析草藥粉末中的藥物 30
3.1.3 TD-ESI/MS分析中草藥粉末樣品的偵測極限 33
3.1.4 分析草藥丸中的藥物 34
3.1.5 中藥粉末樣品LC-MS/MS驗證 36
3.3 第二部分 :以TD-ESI/MS快速測定生物基質中的未標示藥物 38
3.2.1 洗胃引流液樣品檢測 38
3.2.2 血清樣品檢測 39
3.2.3 半定量與定量分析探討 40
3.2.4 TD-ESI/MS分析洗胃引流液及血清樣品的偵測極限 42
3.2.5 重複性探討 43
3.2.6洗胃引流液樣品LC-MS/MS驗證 44
3.2.7 SPME吸附時間探討 48
3.2.8 SPME-TD-ESI/MS分析血清樣品中的藥物 49
3.2.9 SPME半定量分析探討 50
3.2.10 以SPME-TD-ESI/MS分析血清樣品的偵測極限 51
3.2.11 不同分析方法周轉時間比較 52
第四章 結論 53
第五章 參考文獻 55
第六章 附錄 61
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