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研究生:邱靜怡
研究生(外文):Ching-yi Chiu
論文名稱:液相層析串聯質譜技術在生物檢體分析的應用
論文名稱(外文):The Analysis of Biological Specimens by Liquid Chromatography with Tandem Mass Spectrometry
指導教授:許垤棋
指導教授(外文):Dey-chyi Sheu
口試委員:許垤棋
口試委員(外文):Dey-chyi Sheu
口試日期:2015-07-23
學位類別:碩士
校院名稱:大同大學
系所名稱:生物工程學系(所)
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:67
中文關鍵詞:血漿液相層析質譜
外文關鍵詞:Liquid chromatographyMass spectrometryPlasma
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本研究主要是利用液相層析串聯質譜技術來分析血漿中抗癌藥物Irinotecan與其代謝物之濃度,分別針對兩種不同化合物研發出適當的樣品前處理步驟及定量確效方法。
樣品加入內標準品,經由蛋白沉澱法前處理,再以液相層析串聯質譜儀分析。定量分析血漿中Irinotecan濃度,以1/x加權迴歸分析,建立1~500 ng/mL檢量線;血漿中Irinotecan M3濃度,以1/x加權迴歸分析,建立0.1~40 ng/mL檢量線。
藉由確效實驗結果,可確認定量分析方法的準確性與再現性皆符合規範。經Within-run與Between-run的結果得知,LLOQ(Lower Limit of Quantification)之精確度與準確度皆未超出20.0%;其它濃度之精確度與準確度皆於15.0%以內。藥物於血漿中的安定性試驗結果亦符合規範。如此,才能確保此定量分析方法符合Irinotecan及其代謝物於生物檢品分析可接受之標準。
This work was aimed to analyze the concentration of anti-cancer drug Irinotecan and its metabolite in the blood plasma using liquid chromatography mass spectrometry. A pretreatment step and a quantitative validation method for the two different compounds were developed, respectively.
Samples were spiked with internal standard, processed by protein precipitation extraction and analyzed using reversed phase HPLC with MS/MS detection. A linear calibration curve 1~500 ng/mL was created using 1/x weighted regression analysis for the quantitative determination of Irinotecan concentration in the plasma, and an 0.1~40 ng/mL linear calibration curve was created using 1/x weighted regression analysis to quantitatively determine Irinotecan M3 concentration in the plasma.
Based on the validation results, the quantitative analysis method could be ensured, in which the accuracy and reproducibility were in compliance with specifications. The validation analysis of Within-run and Between-run demonstrated that the precision and accuracy for LLOQ(Lower Limit of Quantification)was not deviate by more than 20.0% while those for other concentrations were within 15.0%. The stability test results of drugs in the plasma were also in compliance with specifications. So the quantitative analysis method could conform to the acceptance criteria for analysis of Irinotecan and its metabolites in biological samples.
謝誌I
中文摘要II
AbstractIII
目錄V
第一章 緒論1
1-1 前言1
1-2 研究目的2
第二章 理論3
2-1 藥物動力學3
2-1.1 血中最高濃度及時間(Cmax,Tmax)4
2-1.2 血中濃度與時間之曲線下面積 (Area Under the Curve, AUC)4
2-1.3 清除率(Clearance Index,CI)4
2-1.4 分布體積(Volume of Distribution,Vd)5
2-1.5 半衰期(Half-life,t1/2)5
2-1.6 生體可用率(Bioavailability,F)5
2-2 液相層析串聯質譜分析技術7
2-2.1 液相層析法8
2-2.2 電噴灑游離質譜法13
2-2.3 串聯質譜16
2-2.4 質譜特性21
2-2.5 質譜應用21
2-3 Irinotecan22
2-4 分析方法確效24
2-4.1 準確性(Accuracy)24
2-4.2 精確度(Precision)25
2-4.3 選擇性(Selectivity)26
2-4.4 安定性(Stability)27
第三章 材料與方法29
3-1 實驗儀器29
3-1.1 液相層析串聯質譜儀(Liquid Chromatographic-tandem Mass LC-MS/MS)29
3-1.2 其它儀器29
3-2 實驗藥品30
3-3 標準品配製31
3-3.1 Irinotecan / Irinotecan M3原儲存溶液(Primary Stock Solution)的製備31
3-3.2 Betaxolol內部標準品原儲存溶液的製備32
3-3.3 Irinotecan / Irinotecan M3 檢量線(Calibration Standards)及品管(Quality Control)樣品的配製33
3-4 樣品萃取程序(Sample Extraction Procedure)34
3-4.1 Irinotecan樣品萃取程序34
3-4.2 Irinotecan M3樣品萃取程序37
3-5 液相層析串聯質譜儀條件39
3-5.1 Irinotecan液相層析條件39
3-5.2 Irinotecan M3液相層析條件40
3-5.3 串聯質譜儀分析條件41
第四章 結果與討論42
4-1 質譜圖42
4-2 線性迴歸分析(Regression Analysis)45
4-3 方法確效結果46
4-3.1 精確性及準確性(Precision and Accuracy)46
4-3.2 選擇性(Selectivity)51
4-3.3 安定性(Stability)53
4-4 真實檢品分析(Real Samples Analysis)59

4-5 藥動及分佈分析(Pharmacokinetics and Biodistribution Data Analysis)61
第五章 結論63
參考文獻64
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