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研究生: 陳慧雯
Chen, Huei-Wun
論文名稱: 利用親水性作用層析串聯質譜技術定量食品及血清中的糖化終產物
Quantification of Advanced Glycation End Products in Food and Serum using Hydrophilic Interaction Chromatography - Tandem Mass Spectrometry
指導教授: 陳頌方
Chen, Sung-Fang
口試委員: 陳頌方
Chen, Sung-Fang
葉宛儒
Yeh, Wan-Ju
林嘉和
Lin, Chia-Her
華國泰
Hua, Kuo-Tai
曾素香
Tseng, Su-Hsiang
口試日期: 2024/07/31
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2024
畢業學年度: 112
語文別: 中文
論文頁數: 70
中文關鍵詞: 糖化終產物CMLCELpentosidine親水性作用層析液相層析串聯質譜儀
英文關鍵詞: Advanced glycation end products, CML, CEL, pentosidine, HILIC, LC-MS/MS
研究方法: 實驗設計法
DOI URL: http://doi.org/10.6345/NTNU202401783
論文種類: 學術論文
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  • 糖化終產物(Advanced glycation end products, AGEs)為具有高度異質性的一群化合物,會對人體造成發炎、氧化壓力等相關毒性。本研究為用液相層析串聯質譜儀(LC-MS/MS)分析糖化終產物中常見的生物標記N ε-(羧甲基)離胺酸(Nε-(1-Carboxymethyl)-L-lysine, CML)、N ε-(羧乙基)離胺酸(Nε-(1-Carboxyethyl)-L-lysine, CEL)及戊糖素(pentosidine),對食品及血清樣品進行定量。對於前處理是使用Oasis MCX (Mixed Cation-Exchange)固相萃取(Solid Phase Extraction, SPE)管柱進行AGEs的萃取,以達到最大的分析物回收率。層析管柱的選擇上則是使用親水性作用層析管柱HILIC silica column分離高極性的CML、CEL及pentosidine,以乙腈和水作為移動相,並添加了5 mM的甲酸銨以改進峰型,分離過程中均無離子配對試劑(ion-pairing reagent)的使用。對於本研究開發之分析方法,線性範圍(1~1000 ng/mL)之決定係數R2 > 0.995,同時具有良好的精密度(RSD < 11.00%)以及準確度(82.40 -113.67%),證實能夠準確定量不同食品及血清樣品中的AGEs。定量結果顯示經過烘烤後的Labdiet 5010食品具有較高的AGEs含量(CML, 20.78 μg/g;CEL, 21.53 μg/g),且其含量顯著性地高於未經加熱處理之食品,並且當小鼠攝入經過烘烤後的Labdiet 5010食品時,其體內血清呈現較高的AGEs含量,並且與攝入未經加熱處理食品之小鼠相比,其含量也有顯著性地增加(CML, 3.93 μM;CEL, 9.72 μM) (以上p值皆小於0.05)。

    Advanced glycation end products (AGEs) are a heterogeneous group of compounds that can cause inflammation, oxidative stress, and other toxic effects in the human body. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of common AGEs biomarkers Nε-(1-Carboxymethyl)-L-lysine (CML), Nε-(1-Carboxyethyl)-L-lysine (CEL), and pentosidine. They were quantified in food and serum. Oasis MCX solid phase extraction (SPE) cartridges were used for AGEs extraction to achieve maximum analyte recovery. A hydrophilic interaction chromatography (HILIC) silica column was used to separate the highly polar CML, CEL, and pentosidine. The mobile phase consisted of acetonitrile and water with 5 mM ammonium formate. No ion-pairing reagents were used during the separation. The developed method proved to be linear in the range of 1-1000 ng/mL with coefficients of determination, R2 > 0.995 for all analytes. It also exhibited good precision (RSD < 11.00%) and accuracy (82.40 -113.67%), indicating its ability to accurately quantify AGEs in various food and serum. Quantitative results showed that the AGEs content in food was significantly increased after high-temperature processing (CML: 20.78 μg/g; CEL: 21.53 μg/g), followed by a similar increase in serum AGEs in mice (CML: 3.93 μM; CEL: 9.72 μM) (All p values < 0.05).

    謝誌 i 中文摘要 ii Abstract iii 目錄 iv 表目錄 vii 圖目錄 viii 第一章 緒論 1 第一節 糖化終產物 1 一、 糖化終產物之來源與生成機制 1 二、 AGEs的分類 3 三、 食品中的AGEs 5 四、 AGEs對人體的危害及預防 6 五、 AGEs之常見檢測技術 8 第二節 樣品前處理 10 一、 AGEs的萃取 10 二、 固相萃取(SPE)技術 11 三、 MCX固相萃取 13 第三節 高效液相層析技術 14 一、 液相層析分離原理與各項技術之介紹 15 二、 層析管柱 17 第四節 質譜儀技術 18 一、 電灑游離法 19 二、 三段四極桿串聯式質譜儀 20 三、 多重反應監測之定量分析 22 第二章 實驗材料與分析方法 23 第一節 實驗試劑與材料 23 第二節 實驗樣品 24 第三節 實驗設備 25 第四節 實驗方法 26 一、 實驗設計與前處理 26 二、 高效液相層析參數設定 30 三、 質譜儀參數設定 31 四、 校正曲線之繪製 32 五、 方法確效 33 六、 統計學分析 35 第三章 結果與討論 36 第一節 優化高效液相層析參數 36 一、 層析管柱優化 36 二、 移動相的選擇與優化 39 三、 梯度優化 41 四、 流速優化 43 第二節 優化質譜儀參數 46 一、 離子源參數 46 二、 離子對的選擇與電壓優化 47 第三節 方法確效 50 一、 檢量線 50 二、 準確度與精密度 52 第四節 定量食品與血清之AGEs 53 一、 定量結果 53 二、 統計學分析結果 56 三、 與過去文獻之比較 58 第四章 結論與未來展望 60 參考文獻 61

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