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研究生:游孟儒
研究生(外文):Meng-Ju Yu
論文名稱:動物用藥於液相層析電灑質譜之訊號改善研究
論文名稱(外文):Signal Enhancement of Veterinary Drug Residues Analysis by LC-ESI-MS/MS
指導教授:何國榮何國榮引用關係
指導教授(外文):Guor-Rong Her
口試委員:魏國晉賴建成
口試委員(外文):Guor-Jien WeiChien-Chen Lai
口試日期:2015-07-23
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:化學研究所
學門:自然科學學門
學類:化學學類
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:116
中文關鍵詞:胺基醣苷類化合物電泳淌度控制裝置離子對試劑七氟丁酸超高效能液相層析管柱後分流乙型受體素化合物數據取點數量
外文關鍵詞:Aminoglycosidselectrophoretic mobility control deviceion pairing reagenthqptafluorobutyric acidultra performance liquid chromatographypost column splittingβ-agonistssampling rate
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第一篇:
胺基醣苷類化合物 (aminoglycoside) 屬於高極性化合物。當使用逆相液相層析串聯質譜儀之分析方法需加入全氟羧酸離子對試劑,以提高分析物和靜相之作用力得到更好的分離效果,但離子對試劑之動相溶液具高表面張力和高導電度的特性,會使噴灑不穩定,且其和分析物形成離子對,造成分析物呈現似中性,使胺基醣苷類化合物游離化效率下降,而抑制分析物之訊號。
本研究利用一體式電泳淌度控制裝置 (electrophoretic mobility control device, EMC device) 和液相層析儀 (liquid chromatography, LC) 及電灑質譜儀 (electrospray ionisation mass spectrometry, ESI-MS) 串聯 (LC-EMC-ESI-MS),本裝置藉由施加正電場於銜接管,使帶正電荷之分析物可進入質譜儀偵測;帶負電荷之七氟丁酸成功回退於分流槽內不進入銜接管;且在液相層析傳輸管和銜接管之間保留一適當間距,避免七氟丁酸受到液相層析儀之流速 (0.2 mL/min) 而衝入銜接管內。以此裝置減緩七氟丁酸進入電灑質譜儀,以提升胺基醣苷類化合物之訊號感度卻不失其解析度,並且將此裝置用於檢測牛奶檢體,確認此裝置於食品中胺基醣苷類化合物之檢測及應用性。
在本實驗得到一體式電泳淌度控制裝置之間距為300 μm及1500 V/cm的電場可成功將七氟丁酸回退且得到良好的胺基醣苷類化合物訊號;檢測牛奶檢體得到回收率為86-105 %,定量極限為2-4 ppb,確認此裝置可用於食品樣品中胺基醣苷類化合物的檢測且具有良好之感度。


第二篇:
超高效能液相層析法 (ultra performance liquid chromatography, UPLC) 使用1.7 μm之填充顆粒管柱,管柱內徑為2.1 mm,其最佳流速為0.6 mL/min,此流速下可提供較佳的管柱效能及解析度,並有更快的分析速度。本研究將超高效能液相層析電灑質譜法操作在最佳線性流速,結合管柱後分流 (post column splitting) 的方式,使進入電灑質譜法的移動相流速為最佳噴灑的流速,達到低流速的感度及高流速的解析度與快速分析的訴求。
本實驗以七種乙型受體素化合物進行分析,在超高效能液相層析以0.6 mL/min的移動相流速進行沖提,結合管柱後分流以分流比3:1,使移動相以0.2 mL/min的流速進入游離源進行氣化、離子化。
解析度部分,藉由改變數據取點數量,使流速為0.6 mL/min未分流之解析度比0.2 mL/min的流速佳,且0.6 mL/min經過分流後仍可維持良好之解析度。感度部分,沖提流速為0.6 mL/min分流進入電灑質譜法偵測的感度比未分流佳,但未能達到沖提流速為0.2 mL/min未分流之感度,推測是由於質譜偵測器於高流速偵測下,離子由離子源傳送入質譜儀速度之限制,導致分流方法達不到預期感度。


Part 1
Aminoglycosides are highly polar compounds. Usually, the analysis of aminoglycoside is performed by reversed phased liquid chromatography (RPLC) with haptafluorobutyric acid (HFBA) as ion pairing reagent. HFBA reagent can improve resolution, but it results in suppression of analytes by unstable spray and decreasing ionizing effect.
In this study, an integrated electrophoretic mobility control (EMC) device was developed to increase the sensitivity of aminoglycosides on the liquid chromatography-electrospray ionization mass spectrometry (LC-EMC-ESI-MS). By applying a positive electric field, HFBA anion is retained in the junction reservoir and aminoglycosides cation is able to move forward into mass spectrometry interface. A gap is between LC transfer and connecting capillary for retaining HFBA to avoid flowing into connecting capillary with the flow rate of 0.2 mL/min. The integrated electrophoretic mobility control device with a gap, 300 μm and the electric field , 1500 V/cm, is able to enhance S/N ratio without losing resolution. Therefore, EMC device successfully alleviate ion suppression caused by HFBA. The recoveries range from 86% to 105 %, and the limit of quantitation, LOQ, were found in the range of 2-4 ppb for milk sample.


Part 2
The particle size of ultra performance liquid chromatography (UPLC) column packing is 1.7 μm. According to the Van Deemter equation, it is able to work at higher flow rate (0.6 mL/min) with the 2.1 mm I.D. column. The flow rate is critical for high speed and separation efficiency. However, high flow rate will decrease the ionization efficiency.
In this study, seven β-agonists were analyzed by UPLC. The flow rate of mobile phase was 0.6 mL/min. Using post column splitting (split ratio3:1), a flow rate of 0.2 mL/min was introduced into the ESI-MS system for detection.
The elution flow rate of 0.6 mL/min was better than 0.2 mL/min by increasing sampling rate. UPLC-ESI-MS/MS with post column splitting (0.2 mL/min) provided better sensitivity that of the flow rate 0.6 mL/min without splitting. However, post column splitting did not achieve the sensitivity under 0.2 mL/min without splitting. One possible reason is the limitation in the rate of transferring the ions from ESI source to the mass spectrometer.


中文摘要 i
Abstract iii
目錄 v
圖目錄 viii
表目錄 x
第一篇:胺基醣苷類於液相層析電泳淌度控制裝置質譜法之訊號改善研究 1
第1章 緒論 1
1.1 前言 1
1.2 胺基醣苷類簡介 3
1.3 毛細電泳 4
1.3.1 電滲流 4
1.3.2 電泳淌度 5
1.4 電噴灑游離法 7
1.4.1 電灑法的發展 7
1.4.2 電灑法的原理 7
1.5 電灑法的離子抑制 11
1.5.1 離子抑制的原因 11
1.5.2 減緩離子抑制的方法 12
1.6 線性離子阱質譜儀 16
1.7 研究目的與方法 18
第2章 實驗 29
2.1 實驗藥品 29
2.2 儀器裝置 30
2.2.1 電泳淌度控制裝置製作 30
2.2.2 拉尖電灑噴頭的製作 30
2.2.3 液相層析系統 30
2.2.4 離子阱質譜儀 31
2.2.5 聚合物固相萃取管柱 31
2.2.6 氮氣濃縮儀 32
2.3 實驗方法 33
2.3.1 樣品配製 33
2.3.2 液相層析串聯電泳淌度控制裝置串聯電灑質譜儀架設 33
2.3.3 離子阱質譜儀參數設定 34
2.3.4 牛奶檢體前處理方法 34
第3章 結果與討論 43
3.1 胺基醣苷類化合物於七氟丁酸之抑制 44
3.2 七氟丁酸回退電場之探討 45
3.3 最佳化一體式電泳淌度控制裝置 46
3.3.1 銜接管施加電場之探討 46
3.3.2 液相層析傳輸管與銜接管之間距探討 47
3.4 牛奶檢體中胺基醣苷類化合物之分析 48
3.4.1 牛奶檢體中胺基醣苷類化合物之回收率 48
3.4.2 牛奶檢體中胺基醣苷類化合物之線性範圍 49
3.5 結論 51
參考文獻 65
第二篇:乙型受體素於超高效能液相層析電灑質譜法之訊號改善研究 70
第1章 緒論 70
1.1 前言 70
1.2 乙型受體素簡介 72
1.3 液相層析的發展 73
1.4 串聯式四極矩式質譜儀 75
1.5 研究目的與方法 76
第2章 實驗 82
2.1 實驗藥品 82
2.2 儀器裝置 83
2.2.1 超高效能液相層析系統 83
2.2.1.1 串聯式四極矩式質譜儀 83
2.2.1.2 紫外光偵測器 84
2.3 實驗方法 85
2.3.1 樣品配製 85
2.3.2 分流裝置設計 85
2.3.3 超高效能液相層析電灑質譜結合管柱後方流分析方法 85
第3章 結果與討論 94
3.1 解析度之探討 95
3.1.1 七種乙型受體素於UPLC-MS/MS及UPLC-UV偵測 95
3.1.2 電灑法擴散之探討 96
3.1.3 數據取點數量之探討 96
3.2 感度之探討 98
3.2.1 數據取點數量之探討 98
3.2.2 dwell time之探討 98
3.3 結論 100
參考文獻 114


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