由於元素的不同物種型態具有不同特性，對於生物體來說其作用也大不同，因此真實樣品中的物種分析是相當重要的，可以幫助了解不同物種間的分佈情形，避免對樣品的性質造成誤判。感應耦合電漿質譜儀（Inductively coupled plasma mass spectrometry, ICP-MS）對於元素分析來說是一個具有高靈敏度、線性範圍廣及同位素分析的元素選擇性儀器，適合應用於真實樣品的分析。由於樣品進入 ICP 後會先經過原子化的步驟，所以使得ICP-MS無法分辨同一元素的不同物種，因此在做物種分析的時必須搭配分離技術進行物種分離。液相層析（Liquid chromatography, LC）具有高分離效率、低樣品載入量、高重複性及高再現性等優點，此研究中使用液相層析做為分離系統分別對砷物種以及鈷物種進行分離及分析應用。
第一部份研究中針對砷物種含量進行分析，砷為一種有毒元素，其不同物種具有不同的毒性，目前在工業上仍然被廣泛地使用，若廢棄物處理不慎進入環境中可能經由食物鏈進入生物體進而累積放大而危害到人體，因此本篇利用陰離子交換樹脂層析法（Anion-exchange chromatography）結合ICP-MS 對魚肉當中的砷物種型態及含量進行研究。本實驗系統在最適化條件下能夠在8分鐘內分離 6 個砷物種，波峰面積及高度RSD小於5.1%、偵測極限為0.005-0.011 μg L-1。真實樣品對不同養殖方式的吳郭魚及標準參考樣品做分析，利用甲醇/動相A[ 1%甲醇、0.5 mM碳酸銨、pH值8.5 ]混合液以及1% 硝酸作為萃取試劑結合微波輔助萃取，萃取效率皆可達94% 以上，並在萃取前添加砷物種，確認物種不會進行形態轉換，證實此萃取方法的可行性。
第二部份研究對鈷物種進行分析，鈷是一種有毒元素，當人體攝入過多的鈷則會導致鈷中毒引發中樞神經受損、心血管衰弱及四肢無力顫抖等現象；但是鈷也是人體必需的元素之一，人體必須物質維生素B12就是由鈷為核心的複合體結構，所以維生素B12又被稱為鈷胺素（Cobalamin），核心鈷可以接上不同官能基而有不同衍生物。第二篇研究採用逆相層析法（Reversed phase chromatography）對鈷胺素有機大分子進行分離，由於鈷胺素與管柱作用力極強需使用高濃度的乙腈沖堤使得電漿不穩定並壓抑訊號，所以在管柱後連接上薄膜去溶劑系統（Membrane desolvation sample introduction system, Aridus）去除高有機溶劑。本實驗系統在最適化條件下能夠在15分鐘內分離5個鈷物種，波峰面積及高度RSD小於4.5%、偵測極限為0.007-0.031 μg L-1。真實樣品則是對市面上販售的功能性飲料、營養補給品和海藻等樣品進行分析，以0.5% 硝酸作為萃取試劑結合微波輔助萃取，萃取效率皆可達91-98% 之間，並在萃取前添加Cobalt(II)、Hydroxycobalamin、Cyanocobalamin等三個較穩定的鈷物種，添加回收率皆可達94-101% 之間，確認物種不會進行形態轉換，證實此萃取方法的可行性。

The purpose of the first study was to assess the arsenic species content in the fishes and hoped for using the principal component analysis (PCA) to discriminate the different fishes. The determination of arsenic species in fishes was performed using ion exchange chromatography on a PRP X-100 column with inductively coupled plasma mass spectrometry detection after two step microwave assisted extraction. The arsenic species studied were arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB) and arsenocholine (AsC). Chromatographic separation of all the species was achieved in <8 min in gradient elution mode using (NH4)2CO3 and methanol at pH 8.5. The six extraction methods on arsenic extraction recoveries was evaluated in real sample. The recovery of arsenic species with the two step extraction ( MeOH / Mobile phase A and 1% nitric acid) in real samples were up to 94%. The limits of detection were in the range of 0.005−0.011 μg L−1 for various arsenic species based on peak height.
The purpose of the second study was to develop a method for separating the cobalt species and assess the species content in the functional drinks, nutritive supplements and seaweeds. The determination of cobalt species in functional drinks and nutritive supplements was performed using reversed phase chromatography on C8 micropore column with inductively coupled plasma mass spectrometry detection after microwave assisted extraction. The cobalt species studied were cobalt [Co(II)], hydroxocobalamin (OH-Cbl), cyanocobalamin (CN-Cbl), 5’-deoxyladenosylcobalamin (Ado-Cbl) and methylcobalamin (Me-Cbl). The species were separated by using NH4OAc and acetonitrile at pH 4.0 as elution solution, operated in a stepwise mode, yielded well resolved chromatograms of all the species within 15 min. The five extraction methods on cobalt extraction recoveries was evaluated in real sample. The recovery of arsenic species with the two step extraction (0.5% nitric acid) in real samples were up to 91%. The detection limits of the procedure were 0.007−0.031 μg L−1 for various cobalt species based on peak height.

目錄
論文審定書 i
謝誌 ii
摘要 iii
目錄 vi
圖目錄 viii
表目錄 x
縮寫表 xii

第一章 液相層析結合感應耦合電漿質譜儀於魚肉中砷物種分析之應用
壹、前言 1
貳、實驗部分
一、儀器裝置 5
二、試藥與溶液配製 7
參、實驗過程
一、液相層析分離條件探討 9
二、再現性 10
三、校正曲線與偵測極限預估 10
四、真實樣品分析 10
肆、結果與討論
一、液相層析條件最適化探討 17
二、再現性 27
三、校正曲線與偵測極限的預估 27
四、萃取條件 27
五、真實樣品分析 31
伍、未來工作 51
陸、結論 57
柒、參考文獻 58

第二章 液相層析結合感應耦合電漿質譜儀與電噴灑質譜儀於功能性飲料和營養補給品中鈷物種分析之應用
壹、前言 64
貳、薄膜去溶劑進樣裝置及與液相層析之串聯方法 68
參、實驗部分
一、儀器裝置 70
二、試藥與溶液配製 72
肆、實驗過程
一、液相層析分離條件探討 74
二、薄膜去溶劑進樣系統條件探討 74
三、再現性 75
四、校正曲線與偵測極限的預估 75
五、真實樣品分析 75
伍、結果與討論
一、液相層析條件最適化探討 80
二、薄膜去溶劑系統條件最適化探討 87
三、再現性 98
四、校正曲線與偵測極限的預估 98
五、萃取條件 98
六、真實樣品分析 102
陸、結論 105
柒、參考文獻 106

圖目錄
第一章 液相層析結合感應耦合電漿質譜儀於魚肉中砷物種分析之應用
圖1-1 HPLC-ICP-MS之示意圖 6
圖1-2 各砷物種之結構式 11
圖1-3 砷物種於各pH值環境下之化學式及pKa值 12
圖1-4 實驗流程圖 13
圖1-5 樣品萃取流程圖 16
圖1-6 砷物種在不同pH值下之表徵電荷變化圖 18
圖1-7 砷物種在不同pH值下之滯留時間變化圖 19
圖1-8 改變動相pH值對層析分離的影響 20
圖1-9 改變動相B中碳酸銨濃度 22
圖1-10 改變動相中甲醇濃度對層析分離的影響 26
圖1-11 注入5 μg L-1砷物種與100 mg L-1氯離子之層析圖 26
圖1-12 不同萃取方法萃取淡水吳郭魚#1之萃取效率 32
圖1-13 DORM-3萃取層析圖 34
圖1-14 DOLT-3萃取層析圖 36
圖1-15 淡水吳郭魚#1（Oreochromis mossambicus）萃取層析圖 39
圖1-16 淡水吳郭魚#2萃取層析圖 40
圖1-17 淡水吳郭魚#3(野生)萃取層析圖 41
圖1-18 海水吳郭魚#1萃取層析圖 42
圖1-19 海水吳郭魚#2萃取層析圖 43
圖1-20 珍珠石斑（Cichlasoma managuense）萃取層析圖 44
圖1-21 加州鱸魚（Micropterus salmoides）萃取層析圖 45
圖1-22 香魚（Plecoglossus altivelis）萃取層析圖 46
圖1-23 尼羅紅魚（Oreochromis nilotica）萃取層析圖 47
圖1-24 旗魚（Istiophoridae）萃取層析圖 48
圖1-25 魚類暴露於不同砷濃度環境其體內總砷濃度變化 52
圖1-26 各魚種中砷物種含量比例長條圖 53
圖1-27 海洋生物體內砷醣生成過程 54
圖1-28 海洋生物體內砷酸甜菜鹼生成過程 55

第二章 液相層析結合感應耦合電漿質譜儀與電噴灑質譜儀於功能性飲料和營養補給品中鈷物種分析之應用
圖2-1 各種鈷胺素之結構式 66
圖2-2 薄膜去溶劑系統Aridus II儀器構造圖 69
圖2-3 HPLC-Aridus-ICP-MS之示意圖 71
圖2-4 實驗流程圖 77
圖2-5 樣品萃取流程圖 79
圖2-6 改變動相B中乙腈濃度對層析分離的影響 81
圖2-7 改變動相流速對層析分離的影響 83
圖2-8 改變動相A中乙腈濃度對層析分離的影響 85
圖2-9 改變動相切換時間對層析分離的影響 86
圖2-10 改變動相梯度時間對層析分離的影響 88
圖2-11 改變動相B持續時間對層析分離的影響 89
圖2-12 使用Aridus進樣系統探討Sweep gas flow rate 對鈷物種訊號的影響 90
圖2-13 使用Aridus進樣系統探討Oxygen gas flow rate 對鈷物種訊號的影響 92
圖2-14 使用Aridus進樣系統探討Spray chamber temperature對鈷物種訊號的影響 93
圖2-15 使用Aridus進樣系統探討Menbrane temperature對鈷物種訊號的影響 94
圖2-16 注入2 μg L-1的Co(II)、OH-Cbl、CN -Cbl、Ado-Cbl以及Me-Cbl層析圖和Void volume時間 97
圖2-17 以不同萃取試劑萃取海帶根之萃取效率 103
圖2-18 功能性飲料#1層析圖 105
圖2-19 功能性飲料#2層析圖 106
圖2-20 維他命錠萃取層析圖 107
圖2-21 藍綠藻錠萃取層析圖 108
圖2-22 澎湖海菜萃取層析圖 109
圖2-23 日本昆布萃取層析圖 110

表目錄
第一章 液相層析結合感應耦合電漿質譜儀於魚肉中砷物種分析之應用
表1-1 各種含砷化物之LD50 4
表1-2 微波消化步驟設定參數 15
表1-3 HPLC-ICP-MS系統操作條件 25
表1-4 以HPLC-ICP-MS測定1 μg L-1砷物種之滯留時間與分析訊號再現性 28
表1-5 以HPLC-ICP-MS測定砷物種之校正曲線與偵測極限 29
表1-6 砷物種偵測極限之比較 30
表1-7 以HPLC-ICP-MS測定NRCC DORM-3標準參考樣品中砷物種含量 35
表1-8 以HPLC-ICP-MS測定NRCC DOLT-3標準參考樣品中砷物種含量 37
表1-9 不同魚類樣品之砷物種含量及分佈比例 49
表1-10 魚類暴露於不同砷濃度環境其體內砷物種濃度變化 56

第二章 液相層析結合感應耦合電漿質譜儀與電噴灑質譜儀於功能性飲料和營養補給品中鈷物種分析之應用
表2-1 微波消化步驟設定參數 78
表2-2 動相流速對各物種波峰高度與背景高度之比值（S / B）的影響 84
表2-3 HPLC-Aridus-ICP-MS系統操作條件 96
表2-4 以HPLC-Aridus-ICP-MS測定2 μg L-1 鈷物種之滯留時間與分析訊號再現性 99
表2-5 以HPLC-Aridus-ICP-MS測定鈷物種之校正曲線與偵測極限 100
表2-6 鈷物種偵測極限之比較 101
表2-7 HPLC-Aridus-ICP-MS測定功能性飲料#1、#2中鈷物種之含量 111
表2-8 HPLC-Aridus-ICP-MS測定綜合維他命錠及藍綠藻錠中鈷物種之含量
112
表2-9 HPLC-Aridus-ICP-MS測定澎湖海菜及日本昆布中鈷物種之含量 113

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