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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳家揚(Chia-Yang Chen) | |
| dc.contributor.author | Shih-Hsiang Liao | en |
| dc.contributor.author | 廖士翔 | zh_TW |
| dc.date.accessioned | 2022-11-25T05:35:34Z | - |
| dc.date.available | 2023-10-26 | |
| dc.date.copyright | 2021-11-09 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-26 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82086 | - |
| dc.description.abstract | "內分泌干擾物質是一群會影響人體內分泌系統正常運作的化合物。全氟烷基化合物(perfluoroalkyl substances, PFASs)、鄰苯二甲酸酯類(phthalate esters, PAEs)、羥基苯甲酸酯防腐劑類(parabens)、雙酚A及其替代物(BPs)這四群化合物，被廣泛運用在日常用品或食品包裝之中的內分泌干擾物質。人體暴露到這四類化合物的途徑主要來自飲食，其次為皮膚接觸或是呼吸到附著化合物的灰塵顆粒。本研究中使用血清以及尿液樣本，建立以生物偵測方法檢測體內總濃度；血清能夠反映化合物在體內總量之平衡濃度，尿液能顯示暴露後短時間代謝之化合物情況，兩者一起評估人體所有暴露來源之目標化合物累積濃度。生物偵測技術為建立人體全面暴露的方法，能夠得知可能的內在濃度，使評估暴露與健康效應之間的關係更加清楚。 本研究中血清以及尿液樣本來源為國立臺灣大學醫學院附設醫院兒童醫院，於2018年針對7至11歲世代追蹤孩童以及其兄弟姊妹取樣。本研究中共有303位研究個案，並收取265份血清樣本以及298份尿液樣本做定量分析。 本研究定量化合物為：17種全氟烷基化合物、8種鄰苯二甲酸酯類代謝物、4種羥基苯甲酸酯防腐劑類、雙酚A以及5種替代物。使用Waters I-Class極致液相層析(ultra-performance liquid chromatography, UPLC)搭配Waters Xevo TQ-XS串聯式質譜儀，以UniSpray游離源定量分析。14種全氟烷基化合物、8種鄰苯二甲酸酯類代謝物、4種羥基苯甲酸酯防腐劑類、雙酚S和雙酚AF使用Waters CORTECS (30 × 2.1 mm, 1.6 μm)層析液相管柱，有機動相為甲醇，水性動相為0.1%醋酸水溶液(pH 3.26)，梯度流析流速0.4 mL/min，管柱溫度為40°C，層析時間連同管柱再平衡總需10.3分鐘；剩餘3種全氟烷基化合物、雙酚A、雙酚F、雙酚B、雙酚A二環氧甘油醚二水合物等7種化合物，使用Waters BEH C18(50 × 2.1 mm, 1.7 μm)層析液相管柱，有機相仍為甲醇，水性動相為10 mM N-甲基嗎啡林水溶液(pH 9.65)，梯度流析流速0.4 mL/min，管柱溫度為55°C，層析時間連同管柱再平衡總需10.3分鐘。質譜儀端使用多重反應偵測模式(multiple reaction monitoring, MRM)，定量分析以內部標準品校正之標準品回歸線線性範圍在0.5–500 ng/mL，判定係數R2有0.995以上，儀器偵測極限為0.1–1126 fg，儀器定量極限為0.3–8071 fg，顯示有良好靈敏度。在半定量分析中，使用即時直接進樣游離源(direct analysis in real time, DART)搭配Waters Xevo TQ-XS串聯式質譜儀，優化參數包含游離源到MS端入口的距離為3.7 cm，柵電壓400 V，游離源溫度400°C，每次分析皆以同一樣本三重複，並計算其平均值，以校正訊號變動幅度大的問題，每次分析三重複樣本時間為3.35分鐘。 本研究使用的血清及尿液前處理方法皆為實驗室先前開發之方法加以改良。100 μL血清加入含1%甲酸之乙腈(acetonitrile)，經過Ostro 96孔盤萃取後加入20 μL二甲基亞砜(dimethyl sulfoxide)，再經濃縮與甲醇回溶步驟得以上機；150 μL尿液經過β-glucuronidase以及arylsulfatase混合酵素於37℃培養40分鐘，再加入乙腈沉澱蛋白質後，經過Sirocco 96孔盤過濾後加入20 μL二甲基亞砜，再經濃縮與甲醇回溶步驟得以上機。方法確效部分，血清基質效應為68–136%，萃取效率為50–134%；尿液基質效應為45–134%，萃取效率為59–143%。同日和異日之準確度在80–120%，相對偏差大部分皆在20%以內。血清方法偵測極限範圍與定量極限範圍分別為0.5–521 pg/mL與2.1–844 pg/mL (不包含8:2 diPAP 1480 pg/mL以及MEP 1709 pg/mL)；尿液方法偵測極限範圍及定量極限範圍為1.6–344 pg/mL與20.4–926 pg/mL(不包含6:2 PAP 1479 pg/mL以及8:2 PAP 1506 pg/mL)。 定量結果顯示血清中各化合物檢測率大於80%，除PFHxA (19.2%)、PFDoDA (76.2%)、6:2 PAP (71.7%)、8:2 PAP (63.4%、6:2 diPAP (65.7%)、OH-MINCH (0.75%), BPAF (45.7%)、BPB (42.6%)以及BADGE-2H2O (63%)。尿液中各化合物陽性率高於90%，除了PFBA (85.6%)、PFDoDA (59.4%)、PFHxS (81.9%)、6:2 diPAP (80.9%)、8:2 diPAP (40.9%)、OH-MINCH (48.7%)、BPAF (59.4%) 以及BPB (61.7%)。短碳鏈全氟烷基化合物(PFBA、PFPeA、PFBS、PFHxS)在尿液中相較其他全氟烷基化合物有較高的幾何平均濃度(1.24–13.2 μg/g-cr)。PFOA、PFNA、PFHxS以及PFOS在血中相較其他全氟烷基化合物有較高的幾何平均濃度(1.97–4.63 ng/mL)。將四大類內分泌干擾物質各自做血中相關性統計與尿中相關性統計，發現同一類化合物間有著低度至中度正相關存在，表示這群受試者有共同暴露這些化合物的可能性。在同一化合物在血與在尿的濃度相關性中，PAE代謝物與paraben有著顯著的低度正相關，可能表示尿為這兩大類內分泌干擾物質代謝途徑。使用問卷與化合物濃度做單變項分析，結果發現外出使用塑膠餐具、海水魚、牡蠣以及海帶與PFASs有著正相關，包裝飲料和PFASs有負相關；使用乳液、外出使用塑膠餐具與PAE代謝物有正相關，牡蠣和PAE代謝物有負相關；外出使用塑膠餐具、包裝飲料、牡蠣和海帶與BPs有正相關；使用乳液、外出使用塑膠餐具和海帶與parabens有正相關。本研究定量孩童血中與尿中各類化合物濃度結果以及相關性分析，並與問卷內容作單變相分析找出可能的相關暴露來源，提供未來對內分泌干擾物質管控之優先項目，以降低孩童暴露風險。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T05:35:34Z (GMT). No. of bitstreams: 1 U0001-2610202114302500.pdf: 9771131 bytes, checksum: 3c906d243f3abd98fe02f323e3d724ea (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "致謝 i 中文摘要 ii Abstract v Contents viii List of figures xi List of tables xiv Chapter 1. Introduction 1 1.1 Perfluoroalkyl substances (PFASs) 1 1.2 Phthalate esters (PAEs) metabolites 4 1.3 Bisphenol A and Analogs (BPs) 6 1.4 Parabens 8 1.5 Objectives 10 Chapter 2. Methods 12 2.1 Reagents and materials 12 2.2 Sample collection and storage 17 2.3 Sample preparation 18 2.3.1 Serum sample preparation 18 2.3.2 Urine sample preparation 19 2.4 Instrumental analysis 20 2.4.1 Mass spectrometric conditions 21 2.4.2 UPLC conditions 22 2.4.3 DART conditions 23 2.5 Method validation 24 2.5.1 Matrix effect and extraction efficiency 24 2.5.2 Inter-day and intra-day accuracy and precision 25 2.6 Identification, quantitation and data analysis 26 2.7 Quality assurance and quality control 27 2.8 Statistical analysis 28 Chapter 3. Results and Discussion 30 3.1 Direct analysis in real time 30 3.1.1 Optimization of DART parameters 30 3.1.2 LOD and LOQ of DART 31 3.2 Chromatography 34 3.3 Sample preparation 35 3.3.1 Adjustment of sample preparation steps 35 3.3.2 The conditions of specific chemicals 41 3.4 Identification and quantification 43 3.4.1 IDLs, IQLs and range of calibration curves 43 3.4.2 LODs and LOQs 43 3.5 Method validation 46 3.5.1 Matrix effect and extraction efficiency 46 3.5.2 Inter-day and intra-day accuracy and precision 48 3.6 Analysis of real samples 48 Chapter 4. Conclusions 56 Reference 59 Figures 68 Tables 105 Supplements 133 " | |
| dc.language.iso | en | |
| dc.subject | UniSpray游離源 | zh_TW |
| dc.subject | 極致液相層析/串聯式質譜術 | zh_TW |
| dc.subject | 即時直接進樣游離源 | zh_TW |
| dc.subject | 尿液 | zh_TW |
| dc.subject | 血清 | zh_TW |
| dc.subject | 內分泌干擾素 | zh_TW |
| dc.subject | DART | en |
| dc.subject | endocrine disrupting chemicals | en |
| dc.subject | serum | en |
| dc.subject | urine | en |
| dc.subject | UniSpray ionization | en |
| dc.subject | ultra-performance liquid chromatograph/tandem mass spectrometer | en |
| dc.title | 以即時直接分析質譜術與極致液相層析/串聯式質譜術定量血清及尿液中環境荷爾蒙 | zh_TW |
| dc.title | Determination of endocrine disruptors in serum and urine with direct analysis in real time/tandem mass spectrometry and ultra-performance liquid chromatography/ tandem mass spectrometry | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳保中 教授(Hsin-Tsai Liu),陳鑫昌 助理教授(Chih-Yang Tseng),陳美惠 醫師 | |
| dc.subject.keyword | 極致液相層析/串聯式質譜術,UniSpray游離源,即時直接進樣游離源,尿液,血清,內分泌干擾素, | zh_TW |
| dc.subject.keyword | ultra-performance liquid chromatograph/tandem mass spectrometer,UniSpray ionization,DART,urine,serum,endocrine disrupting chemicals, | en |
| dc.relation.page | 208 | |
| dc.identifier.doi | 10.6342/NTU202104231 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-26 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 環境與職業健康科學研究所 | zh_TW |
| dc.date.embargo-lift | 2023-10-26 | - |
| 顯示於系所單位： | 環境與職業健康科學研究所 | |
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