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  • 學位論文

尿液中鄰苯二甲酸(2-乙基己基)酯代謝物之質譜分析研究

Simultaneous determination of di-2-ethylhexyl phthalate metabolites in Human Urine by Mass Spectrometry

指導教授 : 張耀仁

摘要


目前在phthalate的研究,偏重於環境與食品之殘留量分析,鮮見針對體內代謝物與生理影響之評估。有鑑於塑化劑對人體健康的危害,特別是對懷孕期的胚胎、嬰兒與兒童影響遠大於成年人。本研究以可能最易受影響的早產兒,來進行鄰苯二甲酸二(2-乙基己基)酯(DEHP)暴露程度和代謝狀況評估。本研究收集早產兒之尿液,隨後建立質譜分析方法,進行DEHP代謝之指標化合物,藉以評估早產兒代謝能力與DEHP暴露程度,並作為未來生長發育追蹤探討之依據。 實驗首先嘗試以HFBA/HFIP或PFB-Br之化學衍生化,結合GC/NCI/MS以得到足夠之靈敏度。此外亦嘗試發展較簡易之尿液萃取方法,結果發現:液相萃取法可達85.8%以上之回收率,可有效取代繁瑣的固相萃取法。另外,而在最低偵測極限方面: HFBA/HFIP 較 PFB-Br 衍生化法為佳, MEHP、MEHHP及MEOHP的最低偵測極限分別達到0.25、0.5、0.4 ng/mL。最後我們進行早產兒真實檢體之評估,10位加護病房內之新生兒尿液中MEHP、MEHHP及MEOHP 平均值為534.42 、3207.62 、2197.82 ng/mL,而相對於非加護病房(6位)之新生兒尿液平均為123.98 、114.14 、68.75 ng/mL。由DEHP代謝指標物量的比較,可以更肯定的確認加護病房內之新生兒確實暴露於較高之DEHP環境中。

並列摘要


The research of phthalates was often emphasis on the residue in the environment and food science, but rarely research was focus on the influences in internal metabolite and physiology. It is well known the impact of phthalate in human, especially the reproductive and developmental health in infant. In this study, we investigated the neonates that exposure to Di(2-ethylhexyl) phthalate (DEHP) and secondary oxidized DEHP metabolites. Several mass spectrometry methods were developed for determination of the mono-2- ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl- 5-hydroxyhexyl) phthalate (MEHHP). Then the estimation of metabolism about neonates was present. It will help to further explore the growth of children. At first, the study was developed the good sensitivity in GC-NCI/MS by HFBA/HFIP or PFB-Br derivatization for three metabolites of DEHP. Then, Liquid-phase extraction was developed to replace the solid phase extraction. The recoveries of liquid-phase extraction for three phthalate monoesters were estimated better than 85.8%. The limit of detection (LOD) of HFBA/HFIP phthalates were found better than PFB-phthalates, MEHP, MEHHP, and MEOHP were 0.25, 0.5, 0.4 ng/mL, relatively. The objective of this study was to determine whether premature infants. The concentration of MEHP were mean 534.42 ng/mL, MEHHP were mean 3207.62 ng/mL, MEOHP were mean 2197.82 ng/mL in all 10 neonates of neonatal intensive care center. By contrast, the concentration of MEHP, MEHHP, MEOHP were mean 123.98, 114.14, 68.75 ng/mL in all 6 general neonates. This study was provided the more evidence confirming that neonates who undergo intensive therapeutic medical interventions were exposed to higher concentrations of DEHP than the general neonates.

並列關鍵字

Urine DEHP GC-NCI/MS

參考文獻


1.G. Latini, C.D.Felice, G. Presta, A. D. Vecchio, I. Paris, F. Ruggieri, and P. Mazzeo, In utero exposure to di-(2-ethylhexyl) phthalate and duration of human pregnancy. Environ Health Perspect. , 2003. 111(14) 1783-1785.
3.S. Nallii, D.G.Cooper, J.A.Nicell, Biodegradation of plasticizers by Rhodococcus rhodochrous. Biodegradation, 2002. 13, 343-352.
6.J. A. Tickner, T.Schettler, T. Guidotti, M. McCally, and M. Rossi, Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am J Ind Med., 2001. 39, 100-111.
7.F.A. Arcadi, C.Costa, C. Imperatore, A. Marchese, A. Rapisarda, M. Salemi, G.R. Trimarchi, G. Costa, Oral toxicity of bis(2-ethylhexyl) phthalate during pregnancy and suckling in the Long-Evans rat. Food and Chemical Toxicology, 1998. 36, 963-970.
8.L.H. Li, W.F. Jester, Jr., and J.M. Orth, Effects of Relatively Low Levels of Mono-(2-Ethylhexyl) Phthalate on Cocultured Sertoli Cells and Gonocytes from Neonatal Rats. Toxicology and apploed pharmacology, 1998. 153, 258-265.

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