| 研究生: |
何玟穎 Ho, Wen-Ying |
|---|---|
| 論文名稱: |
利用連線固相萃取液相層析串聯質譜法定量人類頭髮中多種鄰苯二甲酸酯代謝物 Simultaneous quantitation of multiple phthalate metabolites in human hair by on-line SPE LC-MS/MS |
| 指導教授: |
廖寶琦
Liao, Pao-Chi |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 環境醫學研究所 Department of Environmental and Occupational Health |
| 論文出版年: | 2020 |
| 畢業學年度: | 109 |
| 語文別: | 英文 |
| 論文頁數: | 46 |
| 中文關鍵詞: | 鄰苯二甲酸酯代謝物 、頭髮 、人體生物監測 、連線固相萃取液相層析串聯質譜法 |
| 外文關鍵詞: | phthalate metabolite, hair, human biomonitoring, on-line SPE LC-MS/MS |
| 相關次數: | 點閱:72 下載:0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
鄰苯二甲酸酯常作為聚氯乙烯(PVC)產品的塑化劑,例如鄰苯二甲酸二甲酯(DMP),鄰苯二甲酸二乙酯(DEP),鄰苯二甲酸二異丁酯(DiBP)和鄰苯二甲酸二-2-乙基己酯(DEHP)皆是經常被使用的塑化劑。隨著塑化劑的大量使用和生產,民眾們更容易暴露到鄰苯二甲酸酯。因此可以通過生物偵測特定的代謝物來進行暴露評估。頭髮因為可以反映長時間的化學暴露時間,所以已越來越常被作為尿液的替代基質。因此開發一個利用頭髮作為非侵入性樣品來評估人體對鄰苯二甲酸酯暴露的生物偵測方法是非常必須的。在分析之前,將頭髮樣品去污並均質化。此外,使用5%TFA / MeOH(0.5:9.5,v / v)和15%TFA / UPW(1.5:8.5,v / v)兩種溶液進行固-液萃取,之後將兩者的萃取物結合且無需進行葡萄醣醛酸水解,然後使用連線固相萃取(SPE)液相層析串聯質譜法(LC-MS / MS)進行定量。最佳化後的方法針對線性、基質效應、偵測極限/定量極限、精密度以及準確度進行驗證。所有的目標代謝物均得到符合標準的結果。將此驗證方法應用於來自15個健康志願者的真實頭髮樣本之生物偵測研究中,8個代謝物的檢測頻率為100%。在本研究中發現疏水性單酯代謝物更容易摻入到頭髮中。根據本實驗獲得的結果顯示,本開發方法可以檢測頭髮中的鄰苯二甲酸酯代謝物,因此將支持將頭髮作為人類鄰苯二甲酸酯暴露生物監測的替代基質。
Phthalates, such as dimethyl phthalate (DMP), diethyl phthalate (DEP), and di-2-ethylhexyl phthalate (DEHP), are used as plasticizers for polyvinyl chloride (PVC) products. With the extensive usage and production, the public are more likely exposed to phthalates. Exposure assessment can be achieved by biomonitoring specific metabolites. Hair has been increasingly used as a complementary matrix to urine since it could determine the period of chemical exposure after several months to years. Thus, the requirement for the development of biomonitoring schemes using hair as a non-invasive sample to assess human exposure to phthalates is necessary. In this study, a method for the simultaneous measurement of multiple phthalate metabolites in hair samples was developed and validated in this study. Prior to the analysis, the hair samples were decontaminated and homogenized. Further, solid-liquid extraction with of 5% TFA/MeOH (0.5: 9.5, v/v) and 15% TFA/UPW (1.5: 8.5, v/v) then combined the extracts, which not be deconjugated, followed by quantitation using on-line solid phase extraction (SPE) liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed. The optimized method was validated as linearity, limit of detection/limit of quantitation, matrix effects, precision, and accuracy. The optimized method was implemented in the pilot biomonitoring study with authentic hair samples from 15 healthy volunteers. Detection frequencies of 8 metabolites were 100%. More hydrophobic monoester metabolites were found to be preferentially incorporated in hair. The obtained results suggest that the developed method can detect phthalate metabolites in hair, which supports that hair could be used as an alternative matrix in human phthalate exposure biomonitoring.
Alves A, Jacobs G, Vanermen G, Covaci A, Voorspoels S. 2015. New approach for assessing human perfluoroalkyl exposure via hair. Talanta 144:574-583.
Araujo P. 2009. Key aspects of analytical method validation and linearity evaluation. Journal of chromatography B 877:2224-2234.
Boberg J, Christiansen S, Axelstad M, Kledal TS, Vinggaard AM, Dalgaard M, et al. 2011. Reproductive and behavioral effects of diisononyl phthalate (dinp) in perinatally exposed rats. Reproductive Toxicology 31:200-209.
Cappelle D, De Doncker M, Gys C, Krysiak K, De Keukeleire S, Maho W, et al. 2017. A straightforward, validated liquid chromatography coupled to tandem mass spectrometry method for the simultaneous detection of nine drugs of abuse and their metabolites in hair and nails. Analytica chimica acta 960:101-109.
CDC. 2009. Fourth national report on human exposure to environmental chemicals.Atlanta, GA.
Chang YJ, Lin KL, Chang YZ. 2013. Determination of di-(2-ethylhexyl)phthalate (dehp) metabolites in human hair using liquid chromatography-tandem mass spectrometry. Clin Chim Acta 420:155-159.
Chauvin A, Caldelari D, Wolfender JL, Farmer EE. 2013. Four 13‐lipoxygenases contribute to rapid jasmonate synthesis in wounded arabidopsis thaliana leaves: A role for lipoxygenase 6 in responses to long‐distance wound signals. New Phytologist 197:566-575.
Chen H, Feng W, Chen K, Qiu X, Xu H, Mao G, et al. 2019. Transcriptomic analysis reveals potential mechanisms of toxicity in a combined exposure to dibutyl phthalate and diisobutyl phthalate in zebrafish (danio rerio) ovary. Aquatic Toxicology 216:105290.
Choi MH, Kim KR, Chung BC. 2000. Determination of estrone and 17β-estradiol in human hair by gas chromatography–mass spectrometry. Analyst 125:711-714.
Chung BY, Choi SM, Roh TH, Lim DS, Ahn MY, Kim YJ, et al. 2019. Risk assessment of phthalates in pharmaceuticals. Journal of Toxicology and Environmental Health, Part A 82:351-360.
Cooper GA, Kronstrand R, Kintz P. 2012. Society of hair testing guidelines for drug testing in hair. Forensic science international 218:20-24.
Cuypers E, Flanagan RJ. 2018. The interpretation of hair analysis for drugs and drug metabolites. Clin Toxicol (Phila) 56:90-100.
Dewalque L, Pirard C, Vandepaer S, Charlier C. 2015. Temporal variability of urinary concentrations of phthalate metabolites, parabens and benzophenone-3 in a belgian adult population. Environmental Research 142:414-423.
Duty SM, Ackerman RM, Calafat AM, Hauser R. 2005. Personal care product use predicts urinary concentrations of some phthalate monoesters. Environmental health perspectives 113:1530-1535.
Esteban M, Castaño A. 2009. Non-invasive matrices in human biomonitoring: A review. Environment international 35:438-449.
Foster PM. 2006. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. International journal of andrology 29:140-147.
Frederiksen H, Skakkebaek NE, Andersson AM. 2007. Metabolism of phthalates in humans. Molecular nutrition & food research 51:899-911.
Frigerio G, Campo L, Mercadante R, Santos PM, Missineo P, Polledri E, et al. 2020. Development and validation of a liquid chromatography/tandem mass spectrometry method to quantify metabolites of phthalates, including di‐2‐ethylhexyl terephthalate (dehtp) and bisphenol a, in human urine. Rapid Communications in Mass Spectrometry 34:e8796.
Gao D-W, Wen Z-D. 2016. Phthalate esters in the environment: A critical review of their occurrence, biodegradation, and removal during wastewater treatment processes. Science of the total Environment 541:986-1001.
Gao H-T, Xu R, Cao W-X, Qian L-L, Wang M, Lu L, et al. 2017. Effects of six priority controlled phthalate esters with long-term low-dose integrated exposure on male reproductive toxicity in rats. Food and Chemical Toxicology 101:94-104.
Gao W, Kirschbaum C, Grass J, Stalder T. 2016. Lc–ms based analysis of endogenous steroid hormones in human hair. The Journal of steroid biochemistry and molecular biology 162:92-99.
Giovanoulis G, Alves A, Papadopoulou E, Cousins AP, Schütze A, Koch HM, et al. 2016. Evaluation of exposure to phthalate esters and dinch in urine and nails from a norwegian study population. Environmental research 151:80-90.
Grata E, Boccard J, Guillarme D, Glauser G, Carrupt P-A, Farmer EE, et al. 2008. Uplc–tof-ms for plant metabolomics: A sequential approach for wound marker analysis in arabidopsis thaliana. Journal of Chromatography B 871:261-270.
Harkey MR. 1993. Anatomy and physiology of hair. Forensic science international 63:9-18.
He M-J, Lu J-F, Ma J-Y, Wang H, Du X-F. 2018. Organophosphate esters and phthalate esters in human hair from rural and urban areas, chongqing, china: Concentrations, composition profiles and sources in comparison to street dust. Environmental Pollution 237:143-153.
Henderson GL. 1993. Mechanisms of drug incorporation into hair. Forensic Science International 63:19-29.
Heuett NV, Ramirez CE, Fernandez A, Gardinali PR. 2015. Analysis of drugs of abuse by online spe-lc high resolution mass spectrometry: Communal assessment of consumption. Science of the Total Environment 511:319-330.
Hsu J-F, Tien C-P, Shih C-L, Liao P-M, Wong HI, Liao P-C. 2019. Using a high-resolution mass spectrometry-based metabolomics strategy for comprehensively screening and identifying biomarkers of phthalate exposure: Method development and application. Environment international 128:261-270.
Hsu JY, Ho HH, Liao PC. 2015. The potential use of diisononyl phthalate metabolites hair as biomarkers to assess long-term exposure demonstrated by a rat model. Chemosphere 118:219-228.
Huang P-C, Tsai C-H, Liang W-Y, Li S-S, Pan W-H, Chiang H-C. 2015. Age and gender differences in urinary levels of eleven phthalate metabolites in general taiwanese population after a dehp episode. PloS one 10:e0133782.
IARC. 2013. Some chemicals present in industrial and consumer products, food and drinking-water. IARC monographs on the evaluation of carcinogenic risks to humans 101:9.
Jang WJ, Choi JY, Park B, Seo JH, Seo YH, Lee S, et al. 2019. Hair metabolomics in animal studies and clinical settings. Molecules 24.
Jung HJ, Kim SJ, Lee WY, Chung BC, Choi MH. 2011. Gas chromatography/mass spectrometry based hair steroid profiling may reveal pathogenesis in hair follicles of the scalp. Rapid Communications in Mass Spectrometry 25:1184-1192.
Jursa T, Stein CR, Smith DR. 2018. Determinants of hair manganese, lead, cadmium and arsenic levels in environmentally exposed children. Toxics 6:19.
Kamata T, Shima N, Sasaki K, Matsuta S, Takei S, Katagi M, et al. 2015. Time-course mass spectrometry imaging for depicting drug incorporation into hair. Anal Chem 87:5476-5481.
Kato K, Silva MJ, Needham LL, Calafat AM. 2005. Determination of 16 phthalate metabolites in urine using automated sample preparation and on-line preconcentration/high-performance liquid chromatography/tandem mass spectrometry. Analytical chemistry 77:2985-2991.
Katsikantami I, Tzatzarakis MN, Karzi V, Stavroulaki A, Xezonaki P, Vakonaki E, et al. 2020. Biomonitoring of bisphenols a and s and phthalate metabolites in hair from pregnant women in crete. Science of The Total Environment 712:135651.
Koch HM, Gonzalez-Reche LM, Angerer J. 2003. On-line clean-up by multidimensional liquid chromatography–electrospray ionization tandem mass spectrometry for high throughput quantification of primary and secondary phthalate metabolites in human urine. Journal of Chromatography B 784:169-182.
Koch HM, Bolt HM, Angerer J. 2004. Di (2-ethylhexyl) phthalate (dehp) metabolites in human urine and serum after a single oral dose of deuterium-labelled dehp. Archives of toxicology 78:123-130.
Koch HM, Angerer J. 2007. Di-iso-nonylphthalate (dinp) metabolites in human urine after a single oral dose of deuterium-labelled dinp. International journal of hygiene and environmental health 210:9-19.
Koch HM, Becker K, Wittassek M, Seiwert M, Angerer J, Kolossa-Gehring M. 2007. Di-n-butylphthalate and butylbenzylphthalate—urinary metabolite levels and estimated daily intakes: Pilot study for the german environmental survey on children. Journal of Exposure Science & Environmental Epidemiology 17:378-387.
Kronstrand R, Scott K. 2007. Drug incorporation into hair:CRC Press, Boca Raton, USA.
Kucharska A, Covaci A, Vanermen G, Voorspoels S. 2014. Development of a broad spectrum method for measuring flame retardants-overcoming the challenges of non-invasive human biomonitoring studies. Analytical and bioanalytical chemistry 406:6665-6675.
Langer S, Bekö G, Weschler CJ, Brive LM, Toftum J, Callesen M, et al. 2014. Phthalate metabolites in urine samples from danish children and correlations with phthalates in dust samples from their homes and daycare centers. International journal of hygiene and environmental health 217:78-87.
Larabi IA, Fabresse N, Etting I, Nadour L, Pfau G, Raphalen JH, et al. 2019. Prevalence of new psychoactive substances (nps) and conventional drugs of abuse (doa) in high risk populations from paris (france) and its suburbs: A cross sectional study by hair testing (2012-2017). Drug Alcohol Depend 204:107508.
Lessmann F, Schütze A, Weiss T, Langsch A, Otter R, Brüning T, et al. 2016. Metabolism and urinary excretion kinetics of di (2-ethylhexyl) terephthalate (dehtp) in three male volunteers after oral dosage. Archives of toxicology 90:1659-1667.
Lovekamp-Swan T, Davis BJ. 2003. Mechanisms of phthalate ester toxicity in the female reproductive system. Environmental health perspectives 111:139-145.
MacDougall D, Crummett WB. 1980. Guidelines for data acquisition and data quality evaluation in environmental chemistry. Analytical Chemistry 52:2242-2249.
Martín J, Santos JL, Aparicio I, Alonso E. 2016. Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol a, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry. Analytica Chimica Acta 945:95-101.
Minoli M, Casati S, Angeli I, Ravelli A, Rota P, Allevi P, et al. 2019. Analysis of hydroxy-cocaine metabolites as evidence of cocaine consumption: Identification by parent ion search and quantitation by uhplc-ms/ms in hair. Journal of Pharmaceutical and Biomedical Analysis 172:167-174.
Nakahara Y, Kikura R, Takahashi K. 1994. Hair analysis for drugs of abuse viii. Effective extraction and determination of 6-acetylmorphine and morphine in hair with trifluoroacetic acid—methanol for the confirmation of retrospective heroin use by gas chromatography—mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications 657:93-101.
Paluselli A, Fauvelle V, Galgani Fo, Sempéré R. 2018. Phthalate release from plastic fragments and degradation in seawater. Environmental science & technology 53:166-175.
Quinete N, Bertram J, Reska M, Lang J, Kraus T. 2015. Highly selective and automated online spe lc–ms3 method for determination of cortisol and cortisone in human hair as biomarker for stress related diseases. Talanta 134:310-316.
Regulation-(EC). No 1997/2006. Regulation (ec) no. 1907/2006 of the european parliament and of the council of 18 december 2006 concerning the registration, evaluation, authorisation and restriction of chemicals (reach).EU CEC Brussels.
Romero-Franco M, Hernández-Ramírez RU, Calafat AM, Cebrián ME, Needham LL, Teitelbaum S, et al. 2011. Personal care product use and urinary levels of phthalate metabolites in mexican women. Environment international 37:867-871.
Ryu HK, Jung BH, Kim KM, Yoo EA, Woo JT, Chung BC. 2006. Determination of cholesterol in human hair using gas chromatography–mass spectrometry. Biomedical Chromatography 20:999-1003.
Sauvé B, Koren G, Walsh G, Tokmakejian S, Van Uum SH. 2007. Measurement of cortisol in human hair as a biomarker of systemic exposure. Clinical and Investigative Medicine:E183-E191.
Silva MJ, Samandar E, Preau Jr JL, Needham LL, Calafat AM. 2006. Urinary oxidative metabolites of di (2-ethylhexyl) phthalate in humans. Toxicology 219:22-32.
Stöckl D, D’Hondt H, Thienpont LM. 2009. Method validation across the disciplines—critical investigation of major validation criteria and associated experimental protocols. Journal of Chromatography B 877:2180-2190.
Starling AP, Engel LS, Calafat AM, Koutros S, Satagopan JM, Yang G, et al. 2015. Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban shanghai. Environment international 84:94-106.
Sun C, Li M, Gao X, Liu L, Wu X, Zhou J. 2016. Metabolic response of maize plants to multi‐factorial abiotic stresses. Plant Biology 18:120-129.
Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, et al. 2005. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental health perspectives 113:1056-1061.
Tzatzarakis MN, Vakonaki E, Kavvalakis MP, Barmpas M, Kokkinakis EN, Xenos K, et al. 2015. Biomonitoring of bisphenol a in hair of greek population. Chemosphere 118:336-341.
Usman M, Naseer A, Baig Y, Jamshaid T, Shahwar M, Khurshuid S. 2019. Forensic toxicological analysis of hair: A review. Egyptian Journal of Forensic Sciences 9:17.
Van Eeckhaut A, Lanckmans K, Sarre S, Smolders I, Michotte Y. 2009. Validation of bioanalytical lc–ms/ms assays: Evaluation of matrix effects. Journal of Chromatography B 877:2198-2207.
Vogliardi S, Tucci M, Stocchero G, Ferrara SD, Favretto D. 2015. Sample preparation methods for determination of drugs of abuse in hair samples: A review. Analytica chimica acta 857:1-27.
Vogliardi S, Tucci M, Stocchero G, Ferrara SD, Favretto D. 2015. Sample preparation methods for determination of drugs of abuse in hair samples: A review. Anal Chim Acta 857:1-27.
Westgard JO, Lott JA. 1981. Precision and accuracy: Concepts and assessment by method evaluation testing. CRC Critical Reviews in Clinical Laboratory Sciences 13:283-330.
Wongsasuluk P, Chotpantarat S, Siriwong W, Robson M. 2018. Using hair and fingernails in binary logistic regression for bio-monitoring of heavy metals/metalloid in groundwater in intensively agricultural areas, thailand. Environmental research 162:106-118.
Wozniak A, Napierala M, Golasik M, Herman M, Walas S, Piekoszewski W, et al. 2016. Metal concentrations in hair of patients with various head and neck cancers as a diagnostic aid. Biometals 29:81-93.
Yin S, Been F, Liu W, Covaci A. 2019. Hair as an alternative matrix to monitor human exposure to plasticizers - development of a liquid chromatography - tandem mass spectrometry method. J Chromatogr B Analyt Technol Biomed Life Sci 1104:94-101.
Zhao R, Wu Y, Zhao F, Lv Y, Huang D, Wei J, et al. 2017. The risk of missed abortion associated with the levels of tobacco, heavy metals and phthalate in hair of pregnant woman: A case control study in chinese women. Medicine 96:e9388-e9388.