硝基呋喃劑在水產養殖上應用相當廣泛，不論是在藥浴與飼料添加的使用方法上，對於疾病的治療都有很好的功效。由於硝基呋喃對於人體具有致癌性，因此EU在1995年禁止硝基呋喃劑在養殖動物上的使用。本研究開發利用LC-MS/MS分析四種常見的硝基呋喃劑為furazolidone、furaltadone、nitrofurazone與nitrofurantoin，以及將現有硝基呋喃代謝物AOZ、AMOZ、SC與AH的檢測方法做修飾與簡化，而且有良好的方法偵測極限，分別為furazolidone、furaltadone、nitrofurazone、ntrofurantoin、AOZ、AMOZ、SC、AH的6.11、3.63、4.52、6.20、0.23、0.30、0.36、0.53 μg kg-1。光線主要影響硝基呋喃劑貯存標準品穩定性的原因，溫度對於硝基呋喃劑的影響則不顯著。萃取硝基呋喃代謝物時，塑膠離心管的吸附程度與硝基呋喃代謝物的濃度呈現等比例，為了避免待測物因吸附現象而造成樣品回收率降低，以採用玻璃試管為佳。
另一方面，比較以ELISA法與LC-MS/MS法測定吳郭魚肌肉中之AOZ，結果顯示ELISA法在測定低濃度之AOZ殘留時，具有偽陽性的情形出現，以LC-MS/MS法檢測極限達0.05 μg kg-1與108%的回收率，而ELISA法的檢測極限為0.31 μg kg-1與305%的回收率。
本研究針對四種硝基呋喃劑及其代謝物在吳郭魚體內之動力學，分別以不同的給藥方式、濃度與鹽度，以藥物動力學解析吳郭魚體內之肌肉、肝臟、鰓與腸道的藥物殘留濃度。硝基呋喃劑於藥浴給藥結束後24小時，即低於方法偵測極限，以鰓殘留濃度最高，肌肉中的殘留濃度最低。硝基呋喃代謝物殘留於吳郭魚體內各組織，因為肝臟中代謝酵素較其他器官活躍，代謝物以non-bonded的形式存在居多，肌肉與鰓組織則是以bonded代謝物為主。硝基呋喃劑於海水吳郭魚較淡水吳郭魚體內有較高殘留濃度，因海水吳郭魚生存在海水的環境中，以致於減少尿液的排放所造成；吳郭魚體內各組織均具有硝基呋喃劑的代謝分解酵素，硝基呋喃代謝物於魚體內的鰓、血液、肝臟及肌肉中，給藥後立即有代謝物的產生並快速累積的現象。吳郭魚的成熟度是影響代謝物殘留濃度的影響因子之一。對吳郭魚施行藥浴給藥，肝臟是最主要的代謝分解器官，餵食給藥方式則是以腸道為主，而肝臟次之。
本研究針對硝基呋喃劑及其代謝物的分析方法與吳郭魚體內之藥物動力學進行探討，對於過去的樣品前處理方法做修飾與建立完整的方法確效，並且深入瞭解不同環境與給藥方式下，硝基呋喃劑及代謝物在吳郭魚體內分佈、累積與代謝的狀態與速率的差異，建立更完整的藥物動力學資訊，以提供養殖業者以及漁政相關單位參考。

Nitrofurans have been widely used either in waterbath or feed additives for the prevention and treatment of aquatic products. The European Union was able to assign a maximum residue limit and prohibited nitrofurans used to animals in 1995, because of the potential carcinogenic effects of their residues on human health. This study is focusing on the analytical method of four kinds of commonly used nitrofurans and corresponding residual metabolites by LC-MS/MS. The detection limits of furazolidone, furaltadone, nitrofurazone and nitrofurntoin were 6.11, 3.63, 4.52 and 6.20 μg kg-1,respectively. The detection limits of AOZ, AMOZ, SC and AH were 0.23, 0.30, 0.36, 0.53 μg kg-1, respectively. The lightness is the main factor to cause the decomposition of nitrofurans. It is not significant for temperature to depredate nitrofurans. The adsorbtion of metabolites by the plastic tube was in the extraction procedure. Equipments in glass are suggested to be used for the sample pretreatment and plastic meterials are averted to be exercised.
About the comparation of determination of AOZ by ELISA and LC-MS/MS. The result demonstrated that the ELISA method might overestimate the residual AOZ content at low concentrations. The detection limit and recovery of the known addition were 0.05 μg kg-1 and 108% for the LC-MS/MS method and 0.31 μg kg-1 and 305% for the ELISA method, respectively.
The amounts of residual nitrofurans and metabolites in muscle, liver, gill and skin tissue of tilapia which were treated in different conditions were compared. The depletion data of bathing treatment group obtained showed similar be haviors of furazolidone, furaltadone, nitrofurazone, nitrofurantoin in tilapia which the residual time was less than 24 hr. The amounts of residual nitrofurans appeared the highest concentration in gill and the lowest concentration in muscle. Bonded residues of metabolites can be detected for at least 4 weeks after administration in muscle, skin, liver and gill. The concentrations of residual bonded metabolites were higher than non-bonded metabolites in gill and muscle besides liver during depletion periods. After bathing medication, there were more residual nitrofurans and corresponding metabolites in sea water tilapia than fresh water group, because sea water fish survives in high osmotic condition to reduce their urination. Nitrofurans and metabolites were deconstructed by enzyme in gills, livers, intestines and muscles. Then tissues of fish accumulated nitrofurans and metabolites soon after medication. The maturity of fish is one of facters to effect different residual concentration during depletion periods. Liver is the main tissue to deconstruct nitrofurans and metabolites for the bathing medication and intestine is the major tissue to decompose antibiotics for the feeding medicaton.
In this research, we built a completed way to determine nitrofurans and corresponding metatbolites. Comparation of fish in different conditions and different medicative ways were in this investigation. These results could be helpful for aquacultures and government institutions.

摘 要 I
Abstract III
目 錄 V
表目錄 VI
圖目錄 VII

第一章、前言 1
第一節、硝基.喃劑的一般性質 1
第二節、硝基.喃劑的起源與發展 8
第三節、硝基.喃劑及其代謝物檢測方法之相關研究 14
第四節、硝基.喃劑在生物體之藥物動力學相關研究 17
第五節、研究目的 21
第二章、硝基.喃劑及其代謝物分析方法建立及確效 24
第一節、材料與方法 25
第二節、樣品淨化步驟之差異 29
第三節、容器對於硝基.喃代謝物吸附性差異 35
第四節、衍生時間差異 37
第五節、硝基.喃劑及其代謝物之分析方法確效 40
第六節、硝基.喃代謝物之分析方法比較 67
第七節、討論 73
第三章、硝基.喃劑於吳郭魚體內之藥物動力學研究 77
第一節、淡水與海水吳郭魚之藥浴實驗 77
第二節、魚體大小之藥浴實驗 102
第三節、劑量高低之餵食實驗 107
第四節、討論. 120
第四章、結論 126
參考文獻 129
附 錄 142

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