大氣壓力質譜法（Ambient Mass Spectrometry, AMS）是一種可以在大氣壓力下直接進行樣品分析的質譜技術，具有樣品分析時間短、不需要前處理過程或是只需簡單前處理且可快速更換樣品等優勢，因此，近年來陸陸續續有許多新式的大氣壓力游離技術被研發出來。固相微萃取法(Solid Phase Microextraction, SPME)是利用一塗覆高分子吸附物質的熔融矽纖維（Fused silica fiber）與樣品分析物達到吸附-脫附平衡的技術，主要結合了取樣、萃取、濃縮及樣品注入，同時也大幅減少有機溶劑的使用，此方法將樣品前處理的步驟簡化以減少分析時間。

本研究結合固相微萃取法、熱脫附法（Thermal Desorption, TD）及電噴灑游離法（Electrospray Ionization, ESI）技術開發出可快速分析不同樣品之熱脫附電噴灑游離質譜法（TD-ESI/MS），藉由固相微萃取技術進行濃縮、吸附取樣及脫附進樣，來提升熱脫附電噴灑游離質譜法的靈敏度。而SPME-TD-ESI/MS游離技術之操作方式是利用固相微萃取之纖維探針對分析物進行頂空或直接萃取，再將其探針直接插入高溫的熱脫附裝置中，此時吸附在纖維上的分析物因高溫影響而進行熱脫附，產生中性氣相待測分子，其藉由熱氣流帶動到電噴灑離子雲中進行後游離(Post-Ionization)，產生離子-分子反應（Ion-Molecule Reaction, IMR）而得到分析物離子，最後再由質量分析器進行質量的鑑定。

首先，先將本研究所開發的SPME/TD-ESI/MS與先前所開發的TD-ESI/MS進行比較，觀察本研究開發在偵測極限上是否有所改善。而實驗結果顯示，針對4-tert-octylphenol、4-n-nonylphenol及bisphenol A的偵測極限分別為5 ppb、500 ppt及2.5 ppb，相較於TD-ESI/MS其偵測極限分別降低1000、10000及400倍，由此可知，使用SPME/TD-ESI/MS能夠大幅降低偵測極限。接著，SPME/TD-ESI/MS成功地應用在偵測河水中的新興汙染物(4-tert-octylphenol、4-n-nonylphenol及bisphenol A)，在新興汙染物的校正曲線中R2 > 0.997，在再現性的測試中RSD%也皆低於4 %，並定量出愛河河水中的新興汙染物之含量。此外，將SPME/TD-ESI/MS應用在尿液中的藥物濫用(安非他命類藥物及尼古丁)之檢測，相較於TD-ESI/MS此技術能有效降低基質干擾問題，在吸菸者的尿液中可成功地檢測出尼古丁的含量，在含有100 ppb四種安非他命類藥物之尿液中也能順利完成檢測(低於法規陽性檢測值500 ppb)。以上的定量結果皆採用內標準法進行，內標準法的優點在於能避免操作條件變化所造成的誤差，可以同時反應在內標準品和分析物上，如此便可以相互抵消，得到較準確的定量分析。另外，當樣品為複雜基質樣品時（例如：河水、尿液或血液），也能降低其基質干擾問題。


接下來的研究則是改良SPME單一探針取樣方式，發展具多重萃取纖維探針，藉由增加纖維數量以增加靜相吸附體積，在相同萃取時間下提高分析物萃取量，以提高其靈敏度。因此藉由SPME多重探針進行快速取樣，縮短樣品萃取時間並降低偵測極限，相當適合應用在微量分析上。奶瓶若為PC材質，當使用這些奶瓶時會由於材質的關係釋放出Bisphenol A，而採用m-SPME/TD-ESI/MS能夠成功定量出奶瓶中的Bisphenol A的含量，檢測結果在2.3-20.7 ppb之間。

Ambient mass spectrometry (AMS) is known for its fast and direct sample analysis without pretreatment. However, quantitative analysis for most AMS techniques is still a problem because the sampling volumes are inconsistent. Since the amount of analytes extracted by the solid phase microextraction (SPME) fibers dependents on analyte concentration, this feature makes SPME a good tool to perform quantitative analysis for certain chemical compounds in aqueous solution. In this study, we have combined multiple SPME fibers with thermal desorption-electrospray ionization mass spectrometry (TD-ESI/MS) for quantitative study of trace emerging containments in water.

The ambient SPME/TD-ESI/MS consisted of: (1) SPME fibers on a probe for extracting trace chemical compounds in the aqueous solutions; (2) an oven for thermally desorbing the analytes adsorbed on the SPME fibers; (3) an electrospray ionization unit for post-ionizing the desorbed analytes; and (4) a mass spectrometry for detecting the analyte ions. After the analytes established equilibria between the sample matrix and the polymer-coated SPME fibers, the SPME probe was inserted in the preheated oven to desorb the analytes on the fibers. The desorbed analytes were carried by a nitrogen stream into an ESI plume to react with the charged solvent species for ionization. The analyte ions were subsequently detected by a mass spectrometer attached to the TD-ESI source.

The coupling of SPME for sampling and ambient TD-ESI/MS for desorption, ionization and detection was able to achieve a fast, sensitive and accurate quantification for certain emerging containments present in water. The results showed that reproducibility (n=6) for 10 ppb bisphenol A (BPA), 4-tert-octylphenol (4-t-OP) and 4-n-nonylphenol (4-n-NP) was less than 4.0 %. The results of sensitivity test based on the ion signal of 4-n-NP (m/z 219) showed that the detection limit of SPME/TD-ESI/MS on 4-n-NP was as low as 500 ppt. In addition, the capacity of SPME/TD-ESI/MS for the analysis of the river water samples contaminated with BPA, 4-t-OP and 4-n-NP was evaluated, where a good correlation of determination was achieved for each analyte, with R2 values greater than 0.997. Moreover, SPME/TD-ESI/MS was also applied to analyze nicotine and abused drugs in urine. Furthermore, the detection limit was dramatically improved when multiple SPME fibers (n=10) were used for extraction. The results showed that m-SPME/AMS was able to detect BPA in sub ppb level. This technique was also applied to quantitatively evaluate the release bisphenol A from a polycarbonate (PC) baby bottle to the hot water.

目錄
論文審定書 i
謝誌 ii
中文摘要 iv
英文摘要 vi
目錄 viii
圖目錄 xi
表目錄 xv
第一章、緒論 1
第一節、前言 1
第二節、大氣壓力游離質譜法（Ambient Ionization Mass Spectrometry） 5
第三節、熱脫附電噴灑游離法（Thermal Desorption Electrospray Ionization, TD-ESI） 6
第四節、 固相微萃取法（Solid Phase Microextraction, SPME） 8
1. 固相微萃取之簡介 8
2. 固相微萃取纖維種類 12
第五節、固相微萃取法結合質譜分析技術 13
1. 固相微萃取法結合電子游離質譜法（Electron Ionization-Mass Spectrometry, EI-MS） 13
2. 固相微萃取法結合雷射脫附游離質譜法（Laser Desorption Ionization-Mass Spectrometry, LDI-MS） 14
3. 固相微萃取法結合感應耦合電漿質譜法（Inductively Coupled Plasma-Mass Spectrometry, ICP-MS） 15
第六節、固相微萃取法結合大氣壓力游離質譜技術 17
1. 固相微萃取法結合直接電噴灑探針質譜法（Direct Electrospray Probe-Mass Spectrometry, DEP-MS） 17
2. 固相微萃取法結合脫附電噴灑游離質譜法（Desorption Electrospray Ionization-Mass Spectrometry, DESI-MS） 18
3. 固相微萃取法結合直接分析即時游離質譜法（Direct analysis in real time-Mass Spectrometry, DART-MS） 19
4. 固相微萃取法結合脫附電暈束游離質譜法（Desorption corona beam ionization-Mass Spectrometry, DCBI-MS） 20
第七節、論文目標 21
第二章、實驗 22
第一節、實驗設計 22
1. 固相微萃取取樣探針設計 22
2. SPME/TD-ESI/MS的分析流程 25
3. SPME/TD-ESI/MS參數設定 28
第二節、 實驗藥品與試劑 30
1. 試劑 30
2. 藥品 30
第三節、藥品配製 33
第四節、儀器設備 34
第三章、結果與討論 35
第一節、SPME取樣探針結合TD-ESI/MS之開發 35
第二節、以SPME/TD-ESI技術應用於環境中新興汙染物的快速偵測 37
1. 新興汙染物簡介 37
2. SPME萃取時間之探討 40
3. SPME/TD-ESI/MS再現性之探討 43
4. SPME/TD-ESI/MS定量分析之探討 44
5. 以SPME/TD-ESI/MS直接進行愛河中新興汙染物之定量分析 48
第三節、以SPME/TD-ESI技術應用於濫用藥物的快速偵測 51
1. 尼古丁簡介 51
2. SPME萃取方式之探討 52
3. 樣品中添加劑之探討 54
4. SPME纖維種類之探討 56
5. SPME萃取時間之探討 57
6. 以SPME/TD-ESI/MS/MS技術檢測尿液樣品中尼古丁之再現性探討… 59
7. 以SPME/TD-ESI/MS/MS技術檢測尿液樣品中尼古丁之定量分析探討… 61
8. 以SPME/TD-ESI/MS/MS技術對吸菸者尿液中的尼古丁含量進行定量分析 64
9. 以SPME/TD-ESI/MS/MS技術探討吸菸後尿液中尼古丁含量隨時間之變化 66
10. 濫用藥物簡介 69
11. 以SPME/TD-ESI/MS/MS檢測尿液樣品中的安非他命類藥物 70
第四節、多重固相微萃取技術(Multiple SPME)結合TD-ESI/MS之開與與其相關應用 72
1. 探討多重固相微萃取技術之萃取時間 73
2. 不同材質纖維於m-SPME/TD-ESI/MS之探討 76
3. 多重固相微萃取結合TD-ESI/MS技術之優點 78
4. 以m-SPME/TD-ESI/MS檢測奶瓶中的雙酚A 79
第四章、結論 81
第五章、參考文獻 83

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