以大氣壓氣相層析/串聯式質譜儀分析血清與尿液中氟調聚合醇與全氟磺胺類化合物

全氟烷基化合物(perfluoroalkyl substances, PFASs)具有抗油防水的特性，因此被廣泛用於各種工業、民生消費品的製造。然而，它也是目前已知的內分泌干擾物之一，相關的暴露可能會導致人體不良健康效應，例:肝毒性、認知發展障礙。對此，現今已有多國明定規範，限制長碳鏈全氟烷基化合物的使用，取而代之的是具有相似特性之氟調聚合醇類和全氟磺胺類的使用。因此，評估人體此二類物質的內在暴露劑量非常重要，而生物偵測為較合適的方法，血清檢測可反映化學物質平時在人體的濃度，尿液檢測則可指出化學物質短期的代謝情形，故本篇研究以血清和尿液作為生物基質以代表人體的內在劑量。本研究為開發以大氣壓氣相層析/串聯式質譜儀 (atmospheric pressure gas chromatography coupled tandem mass spectrometer, APGC-MS/MS)對於血清及尿液中 4 種氟調聚合醇和 1 種全氟磺胺類物質的分析方法並用於調查我國兒童的暴露情形(265 個血清及 298 個尿液樣本)。本研究最適化 APGC-MS/MS 各項參數並評估基質效應和萃取效率且進行準確度 (accuracy)和精密度(precision)的方法確效。各化學物質在血清中之基質效應(matrix effect)為 81%-96%，萃取效率(extraction efficiency)為 73%-94%;在尿液中之基質效應為 76%-118%，萃取效率為 83%-91%。方法確效的部分，在三種不同濃度下(分別為 10、50 和 100 ng/mL)之回收率(recovery)皆高於 85%且精密度(%CV)皆低於 15% (n = 5)，線性範圍為 0.5-500 ng/mL。此方法已應用於來自臺大兒童醫院 (National Taiwan University Children Hospital, NTUCH)的實際樣本，結果顯示在血液中普遍有檢出 6:2 FTOH、8:2 FTOH 和 10:2 FTOH，而尿液的檢出率相對較低且僅有檢出 8:2 FTOH 和 10:2 FTOH。以濃度資料搭配問卷資料中的「家中是否有鋪設地毯」和「飲料包裝材質」兩部分分別進行 Student’s t-test 檢定，結果皆顯示未有顯著相關性(at p-value < 0.05)，但此二類化學物的代謝物之關注仍須重視。綜合以上，本研究開發的方法適用於血清與尿液中氟調聚合醇與全氟磺胺類化合物的檢測，且此研究是使用大氣壓氣相層析游離/串聯式質譜儀，而非過去多數文獻所使用的液相層析/串聯式質譜儀搭配不同的游離源;本研究分析方法於血清和尿液中 8:2 FTOH 具有較低的方法定量極限，為過去文獻數值的八倍低，意即較好的偵測靈敏度。此方法能提供後續相關的人體暴露評估一些方向以監測人體的暴露情形，協助改善世人的健康狀況。

關鍵字

全氟烷基化合物；氟調聚合醇；全氟磺胺類化合物；大氣壓氣相層析儀；血清；尿液

並列摘要

Perfluoroalkyl substances (PFASs) possess both water- and grease-repelling properties, and thus they are widely used in industrial and consumer products. However, they are also endocrine disrupting chemicals, which may cause adverse health effects, such as liver toxicity and developmental effects. In order to prevent the problems, lots of countries regulate the usage of long-chain PFASs and substituted fluorotelomer alcohols and perfluorinated sulfonamides for long-chain ones in these years because they are short- chain PFASs and also have similar chemical characteristics, which possess oil-resistant and waterproof properties. Therefore, biomonitoring of fluorotelomer alcohols and perfluorinated sulfonamides in human for obtaining the internal doses of human exposure is crucial. The concentrations of chemicals in serum can indicate their common levels in humans and the levels of chemicals in urine can show their metabolic pathways through the human body in short term. So, this study used serum and urine as biological matrices for representing the internal doses of compounds in human bodies. The purpose of the study was to develop an analytical method for determining four fluorotelomer alcohols and one perfluorinated sulfonamides in serum and urine with an atmospheric pressure gas chromatography coupled with a tandem mass spectrometer (APGC-MS/MS) and we also investigated the exposure of children to these chemicals in Taipei (265 serum samples and 298 urine samples). The study optimized APGC-MS/MS parameters, evaluated the matrix effect and extraction efficiency, and finished the method validation for accuracy and precision. The matrix effects and the extraction efficiencies of our target compounds in the serum method ranged from 81%-96% and 73%-94%, respectively. The matrix effects and extraction efficiencies of urine samples ranged from 76%-118% and 83%- 91%, respectively. The results of method validation indicated that the recoveries were all above 85% at three tested levels (10, 50 and 100 ng/mL) and the precisions (%CV) were all lower than 15% (n = 5). The linear calibration ranges of target compounds were 0.5- 500 ng/mL in methanol. This method was used to analyze 265 serum samples and 298 urine samples from the National Taiwan University Children Hospital (NTUCH). The results showed 6:2 FTOH, 8:2FTOH and 10:2 FTOH were found in more than a half of the serum samples; 8:2 FTOH and 10:2 FTOH were found in some urine samples but the positive rates were lower than those in serum samples. We combined the concentration data with the questionnaire information for carpets and beverage packaging to do Student’s t-test. However, the statistical results indicated that there were no significant correlation (at p-value <0.05) but it warrants continuous monitoring because the metabolites of fluorotelomer alcohols and perfluorinated sulfonamides may lead to some diseases. In conclusion, the developed method in this study is suitable for the determination of fluorotelomer alcohols and perfluorinated sulfonamides in serum and urine samples. In the study, we used APGC-MS/MS to do the analysis instead of LC- MS/MS with different ion sources which previous studies used. And we found that limit of quantifications (LOQs) of 8:2 FTOH in serum and urine by this method were lower than former research, which indicated better detection sensitivity of the method. The method can help future survey on fluorotelomer alcohols and perfluorinated sulfonamides for improving human health in the world.

並列關鍵字

perfluoroalkyl substances ； fluorotelomer alcohols ； perfluorinated sulfonamides ； atmospheric pressure gas chromatography ； serum ； urine

參考文獻

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