摘要
多环芳烃(polycyclic aromatic hydrocarbons,简称PAHs)是一类典型的环境持久性有机污染物,在职业高PAHs暴露环境下,容易诱发皮肤癌、肺癌等癌症,现已被多个国家列为优先控制的污染物。评价多环芳烃暴露水平可为环境健康风险预警评价和流行病学研究等提供依据。由于暴露途径以及影响因素复杂多样化,采用尿样中PAHs羟基代谢产物(主要有1-羟基芘、萘酚及菲、芴的代谢产物)作为生物标志物来综合评价人体暴露PAHs污染物的危害及肿瘤风险预警已逐渐成为研究的热点。因此建立PAHs羟基代谢物靶标分析新方法,对PAHs的羟基代谢产物进行代谢物靶标分析以及PAHs羟基代谢产物及其结构类似物的HPLC-FD高通量轮廓谱分析方法,并构建职业暴露PAHs人群的肺癌风险预测模型,对于PAHs所致肺癌预警、早期诊断、职业安全评价和肺癌的分子机制的深入研究有着重要的现实意义。
本文第二章应用一阶导数同步荧光技术联用胶束增敏法建立了同时检测1-羟基芘、1-萘酚、2-萘酚、9-羟基菲和2-羟基芴的新方法。研究表明:在pH 5.0 B-R缓冲溶液中,加入吐温-20作为增敏剂,当选择激发单色器和发射单色器的波长差Δλ= 10 nm,只需一次扫描,利用计算机的导数功能得到一阶导数荧光光谱,可实现五组分的同时鉴别和定量测定。采用峰-零法分别在λ= 389.4 nm、332.4 nm、338.6 nm、355.8 nm、306.0 nm记录1-羟基芘、1-萘酚、2-萘酚、9-羟基菲和2-羟基芴导数荧光强度值。1-羟基芘、1-萘酚、2-萘酚,9-羟基菲和2-羟基芴的线性范围分别为1.75×10~(-9)~ 4.50×10~(-6) mol·L~(-1) , 3.64×10~(-8)~2.20×10~(-4) mol·L~(-1) , 8.18×10~(-9)~1.20×10~(-4) mol·L~(-1) ,3.26×10~(-9)~8.50×10~(-5) mol·L~(-1)和4.88×10~(-9)~5.50×10~(-6) mol·L~(-1) ,检出限分别为5.25×10~(-10) mol·L~(-1),1.10×10~(-8) mol·L~(-1),2.46×10~(-9) mol·L~(-1),9.77×10~(-10) mol·L~(-1)和1.46×10~(-9) mol·L~(-1)。本法快速、灵敏,可同时测定尿样中痕量1-羟基芘、1-萘酚、2-萘酚、9-羟基菲和2-羟基芴,结果与高效液相色谱法一致。
本文第三章应用反相高效液相色谱-荧光-二级管阵列检测器串联建立了同时测定尿中5种多环芳烃和6种羟基多环芳烃的新方法。采用Shim-pack VP - ODS C18柱(150 mm×4.6 mm, 4. 6±0. 3μm)色谱柱分离,以甲醇/乙酸钠-乙酸缓冲液(pH 4.5)(65:35,v/v)为流动相,流速为1.0 mL·min~(-1),柱温为30°C;进样量为20μL。外标法定量,分离效果好,缩短了样品分析时间,30 min内可将11种待测物质完全分离。荧光检测器的检出限为0.001~0.090μmol·L~(-1);二极管阵列检测器检出限为0.050~0.900μmol·L~(-1);样本加标回收率为95.5%~108.0%。已用于尿样测定,结果满意。
本文第四章基于高效液相色谱法建立多环芳烃所致肺癌病人的预测模型。利用第三章建立起的反相高效液相色谱法检测得到36名肺癌病人和10名健康人尿中多环芳烃代谢轮廓谱,结合主成分分析法和偏最小二乘法对所得到的代谢轮廓谱数据进行分析,建立多环芳烃所致肺癌病人的预测模型,并初步筛选并鉴定出2个相对较为重要的具有显著异常改变的指标(1-萘酚,萘),该法对多环芳烃所致肺癌的诊断有一定的参考意义。
Polycyclic aromatic hydrocarbons (PAHs) are a large class of ubiquitous persistent organic pollutants, which may induce skin and lung cancers in occupational settings and have been listed in preferred controlling pollutants by many countries. The evaluation of exposure to PAHs can provide evidence for environmental health risk warning and epidemiological study. However, exposure and influential factors are very complicated, and urinary hydroxyl PAHs which are major metabolites of PAHs in human urine have been widely used as biomarkers for the estimation of health risks as a result of PAHs exposure. Therefore, we develop novel methods for the establishment target analysis of hydroxy metabolites and the high-throughput HPLC-FD profiling analysis of the hydroxy metabolites and their structure analogues, and build lung cancer risk prediction model of occupational exposure to PAHs, it is an important practical significance to looking for PAHs’early warning marker of lung cancer, early dagnosis, occupational safety evaluation and the in-depth study of the molecular mechanism of lung cancer.
In the chapter 2, a novel method of first derivative synchronous fluorescence was developed for the rapid simultaneous analysis of trace 1-hydroxypyrene (1-OHP), 1-naphthol (1-NAP), 2-naphthol (2-NAP), 9-hydroxyphenanthrene (9-OHPe) and 2-hydroxyfluorene (2-OHFlu) in human urine. In the B–R buffer solution of pH 5.0, these five metabolites of PAHs can be simultaneously identified and quantified atΔλ= 10 nm using Tween-20 as a sensitizer. The first derivative synchronous spectra were obtained by spectroscopy software program for spectral acquisition and subsequent calculation of the derivative data using the Savitzky–Golay method. The corresponding first derivative synchronous fluorescence data of 1-OHP, 1-NAP, 2-NAP, 9-OHPe and 2-OHFlu were manipulated atλ= 389.4 nm、332.4 nm、338.6 nm、355.8 nm and 306.0 nm using the peak–zero method, respectively. In the optimal experimental conditions, there was a linear relationship between the fluorescence intensity and the concentration of 1-OHP, 1-NAP, 2-NAP, 9-OHPe and 2-OHFlu in the range of 1.75×10~(-9)~4.50×10~(-6) mol L~(-1), 3.64×10~(-8)~2.20×10~(-4) mol L~(-1), 8.18×10~(-9)~1.20×10~(-4) mol L~(-1), 3.26×10~(-9)~8.50×10~(-5) mol L~(-1) and 4.88×10~(-9) ~5.50×10~(-6) mol L~(-1), respectively. The limits of detection (LOD) were found to be 5.25×10~(-10) mol L~(-1) for 1-OHP, 1.10×10~(-8) mol L~(-1) for 1-NAP, 2.46×10~(-9) mol L~(-1) for 2-NAP, 9.77×10~(-10) mol L~(-1) for 9-OHPe and 1.46×10~(-9) mol L~(-1) for 2-OHFlu. The proposed method is reliable, selective and sensitive, and has been used successfully in the determination of traces of 1-OHP, 1-NAP, 2-NAP, 9-OHPe and 2-OHFlu in human urine samples, whose results were in good agreement with those gained by the HPLC method.
In the chapter 3, a method was presented for the determination of 5 polycyclic aromatic hydrocarbons (PAHs) and 6 hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) by fluorescence and diode array detection - reversed phase high performance liquid chromatographic method. The determination was carried out on a Shim-pack VP - ODS C18 column (150 mm×4.6 mm, 4.6±0.3μm) by 20μL sample and Methanol/HAc- NaAc (pH 4.5) (65:35, V/V ) was used as mobile phase at a flow rate of 1.0 mL min~(-1) and the column oven temperature was set at 30°C. Instrument detection limits of the fluorescence detection were 0.001~0.090μmol L~(-1) and the diode array detection were 0.050~0.900μmol L~(-1), precisions of the method were 0.6~1.4% (fluorescence detection) and 1.1~5.5% (diode array detection). The recoveries of standard addition were 95.5~108.0%. The method is suitable for the identification and quantification of these compositions in human urine.
In the chapter 4, classification models of lung cancer patients and healthy people have been built from high performance liquid chromatography data. The PAHs metabolic profiling from 36 patients with lung cancer and 10 normal adults was determined by RP-HPLC,and analyzed in the methods of principal component analysis and partial least squares, the classification model was built, finally the two more important indicator with relatively significant abnormal changes (1–NAP, NAP) were identified, it is useful for lung cancer diagnoses.
引文
[1] Rey-Salgueiro L, Martínez-Carballo E, García-Falcón M S, et al. Occurrence of polycyclic aromatic hydrocarbons and their hydroxylated metabolites in infant foods[J]. Food Chem, 2009, 115: 814–819.
[2] Santino O, Papuzza V. Levels, fingerprint and daily intake of polycyclic aromatic hydrocarbons (PAHs) in bread baked using wood as fuel[J]. J. Hazard. Mater, 2009, 164: 876–883.
[3] Suzuki N, Hayakawa K, Kameda T, et al. Monohydroxylated polycyclic aromatic hydrocarbons inhibit both osteoclastic and osteoblastic activities in teleost scales[J]. Life Sci, 2009, 84: 482–488.
[4]杨发忠,颜阳,张泽志,等.多环芳烃研究进展[J].云南化工, 2005, 32(2) : 45–48.
[5]王劲,闫卫利,郜舟顺,等.尿中1-羟基芘作为焦炉工多环芳烃暴露生物监测指标的研究[J].河南预防医学杂志, 2006, 17(3): 138–139.
[6]王宇,董玉莲,范瑞芳,等.尿中多种多环芳烃代谢物同时测定的高效液相色谱-荧光检测法[J].环境与健康杂志, 2006, 23(1): 76–78.
[7]段小丽,杨洪彪,张林,等.尿液中多环芳烃羟基代谢产物分析方法研究[J].环境科学研究, 2004, 17(3): 62–65.
[8]牛红云,蔡亚岐,魏复盛,等.多环芳烃暴露的生物标志物—尿中羟基多环芳烃[J].化学进展, 2006, 18 (10):1381–1389.
[9] Hollender J, Koch B, Dott W. Biomonitoring of environmental polycyclic aromatic hydrocarbon exposure by simultaneous measurement of urinary phenanthrene, pyrene and benzo[a]pyrene hydroxides[J]. J. Chromatogr. B, 2000, 739: 225–229.
[10] Maninia P, Palmade G, Mutti A. Exposure assessment at the workplace: implications of biological variability[J]. Toxicol. Lett, 2007, 168: 210–218.
[11] Li Z, Sandau C D, Romanoffa L C, et al. Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population[J]. Environ. Res, 2008, 107: 320–331.
[12] Hansen ? M, Mathiesen L, Pedersen M, et al. Urinary 1-hydroxypyrene (1-HP) in environmental and occupational studies—A review[J]. Int. J. Hyg. Environ. Health,2008, 211: 471–503.
[13] Jongeneelen F J. Benchmark guideline for urinary 1-hydroxypyrene as biomarker of occupational exposure to polycyclic aromatic hydrocarbons[J]. Ann. Occup. Hyg, 2001, 45(1): 3–13.
[14] Jongeneelen F J , Anzion R B M, Henderson P T. Determination of hydroxylated metabolites of polycyclic aromatic hydrocarbons in urine[J]. J. Chromatogr, 1987, 413: 227–232.
[15]段小丽,魏复盛,张军锋,等.人尿中1-羟基芘浓度与多环芳烃日暴露量的关系[J].环境化学, 2005, 24 (1): 86–89.
[16] Kuo C T, Chen H W, Chena J L. Determination of 1-hydroxypyrene in children urine using column-switching liquid chromatography and fluorescence detection[J]. J. Chromatogr. B, 2004, 805(2): 187–193.
[17]匡少平,孙东亚.多环芳烃的毒理学特征与生物标志物的研究[J].世界科技与发展, 2007, 29(2): 41–47.
[18] Preuss R, Koch H K, Wilhelm M, et al. Pilot study on the naphthalene exposure of German adults and children by means of urinary 1-and 2-naphthol levels[J]. Int. J. Hyg. Environ. Health, 2004, 207: 441–445.
[19] Elovaara E, Mikkola J, Makela M, et al. Assessment of soil remediation workers’exposure to polycyclicaromatic hydrocarbons (PAH): Biomonitoring of naphthols, phenanthrols and 1-hydroxypyrene in urine[J]. Toxicol. Lett, 2006, 162: 158–163.
[20] Sancho J V, Cabanes R A, Lopes F J, et al. Direct determination of 1-naphthol in human urine by coupled-colum liquid chromatography with fluorescence detection[J]. Chromatogr, 2003, 58: 565–569.
[21] Preuss R, Angerer J, Drexler H. Naphthalene—an environmental and occupational toxicant[J]. Int. Arch. Occup. Environ. Health, 2003, 76: 556–576.
[22]冷曙光,郑玉新,宋文佳,等.尿中萘及其代谢产物作为焦炉工生物监测指标的研究[J].工业卫生与职业病, 2003, 29 (5): 284–287.
[23] Luan T G, Yu K S H, Zhong Y, et al. Study of metabolites from the degradation of polycyclic aromatic hydrocarbons (PAHs) by bacterial consortium enriched from mangrove sediments[J]. Chemosphere, 2006, 65: 2289–2296.
[24] Jacob J, Seidel A. Biomonitoring of polycyclic aromatic hydrocarbons in human urine[J]. J.Chromatogr. B, 2002, 778: 31–47.
[25]欧阳珏,武明花,黄琛,等.代谢组学及其在恶性肿瘤研究中的应用[J].中南大学学报(医学版), 2007, 32(2): 221–225.
[26]许彬,王海龙,魏开华,等.代谢组学分析技术及其在几类重大疾病研究中的应用[J].分析测试学报, 2006, 25(5):128–132.
[27]吴昊,薛如意,沈锡中.代谢组学在肿瘤诊断应用中的新进展[J].复旦学报(医学版), 2008, 35(4): 926–928.
[28]严士海,朱萱萱.代谢组学在疾病诊断中的应用研究进展[J].现代中西医结合杂志, 2007, 16(5): 711–712.
[29]王文昭,赵欣捷,李响,等.尿中修饰核苷代谢轮廓分析在肺癌诊断中的作用[J].中国医学科学院学报, 2007, 29(16): 738–741.
[30]李海锋,路鑫,鹿洪亮,等.全二维气相色谱/飞行时间质谱(GC×GC-TOFMS)用于烟叶中酸性成分的分离与分析[J].高等学校化学学报, 2006, 27(4): 612–617.
[31] Zhao X J, Zhang Y, Meng X L, et al. Effect of a traditional Chinese medicine preparation Xindi soft capsule on rat model of acute blood stasis: A urinary metabonomics study based on liquid chromatography–mass spectrometry[J]. J. Chromatogr. B, 2008, 873: 151–158.
[32] Lu X, Zhao X J, Bai C M, et al. LC–MS-based metabonomics analysis[J]. J. Chromatogr. B, 2008, 866: 64–76.
[33] Elovaara E, Vaananen V, Mikkola J. Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention withβ-naphthoflavone induction in the rat[J]. Arch. Toxicol, 2003, 77: 183–193.
[34] Kuusimaki L, Peltonen Y, Mutanen P. Urinary hydroxy-metabolites of naphthalene, phenanthrene and pyrene as markers of exposure to diesel exhaust[J]. Int. Arch. Occup. Environ. Health, 2004, 77: 23–30.
[35]饶竹,李松.何淼,等.高效液相色谱–荧光–紫外串联测定土壤中16种多环芳烃[J].分析化学, 2007, 35(7): 954–958.
[36] Preuss R, Angerer J. Simultaneous determination of 1- and 2-naphthol in human urine using on-line clean-up column-switching liquid chromatography-fluorescence detection[J]. J. Chromatogr. B, 2004, 801: 307–316.
[37]张德云,孙成均,王涛.高效液相色谱法测定室内空气中13种多环芳烃[J].华西医大学报, 2002, 33(1): 140–143.
[38] Grainger J, Huang W L, Patterson J D G, et al. Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites[J]. Environ. Res, 2006, 100: 394–423.
[39] Smith C J, Walcott C J, Huang W L, et al. Determination of selected monohydroxy metabolites of 2-, 3- and 4-ring polycyclic aromatic hydrocarbons in urine by solid-phase microextraction and isotope dilution gas chromatography-mass spectrometry[J]. J. Chromatogr. B, 2002, 778: 157–164.
[40] Romanoff L C, Li Z, Young K J, et al. Automated solid-phase extraction method for measuring urinary polycyclic aromatic hydrocarbon metabolites in human biomonitoring using isotope-dilution gas chromatography high-resolution mass spectrometry[J]. J. Chromatogr. B, 2006, 835: 47–54.
[41] Delhommea O, Millet M , Herckes P. Determination of oxygenated polycyclic aromatic hydrocarbons in atmospheric aerosol samples by liquid chromatography - tandem mass spectrometry[J]. Talanta, 2008, 74: 703–710.
[42] Vande-Wiele T R, Peru K M, Verstraete W, et al. Liquid chromatography-mass spectrometry analysis of hydroxylated polycyclic aromatic hydrocarbons, formed in a simulator of the human gastrointestinal tract[J]. J. Chromatogr. B, 2004, 806(2): 245–253.
[43]许金钩,王尊本.荧光分析法[M].北京:科学出版社, 2006: 299–301.
[44]李锐. LC-MS血清代谢组学方法的建立及其在肾病分析中的应用[D].吉林大学, 2007: 28–30.
[45] Yang H M, Wang Y S, Li J H, et al. Synchronous fluorescence determination of urinary 1-hydroxypyrene, 1-naphthol and 9-hydroxyphenanthrene based on the sensitizing effect ofβ-cyclodextrin[J]. Anal. Chim. Acta, 2009, 636: 51–57.
[46] Saitoh T, Itoh H, Hiraide M. Admicelle–enhanced synchronous fluorescence spectrometry for the selective determination of polycyclic aromatic hydrocarbons in water[J]. Talanta, 2009, 79: 177–182.
[47] Benamor M, Aguerssif N. Simultaneous determination of calcium and magnesium by derivative spectrophotometry in pharmaceutical products[J]. Spectrochim. Acta A, 2008, 69: 676–681.
[48] Sánchez Rojas F, Bosch Ojeda C. Recent development in derivative ultraviolet/visible absorption spectrophotometry: 2004–2008 A review[J]. Anal. Chim. Acta, 2009, 635: 22–44.
[49] Blanco C C, García Campaňa A M, Alés Barrero F, Román Ceba M. Micellar medium for the analysis of complex mixtures of molybdenum and tungsten by derivative synchronous spectrofluorimetry in steels[J]. Talanta, 1995, 42: 1037–1044.
[50] Gong Q J, Qiao J L, Du L M, et al. Recognition and simultaneous determination of ofloxacin enantiomers by synchronization–1st derivative fluorescence spectroscopy[J]. Talanta, 2000, 53: 359–365.
[51] Gatellier P, Kondjoyan A, Portanguen S, et al. Determination of aromatic amino acid content in cooked meat by derivative spectrophotometry: Implications for nutritional quality of meat[J]. Food Chem, 2009, 114: 1074–1078.
[52] Sabry S M. Application of computerized compensation method to derivative synchronous spectrofluorimetry. Analysis of floctafenine and floctafenic acid in plasma[J]. Anal. Chim. Acta, 1997, 351: 211–221.
[53] Dave H N, Mashru R C, Thakkar A R. Simultaneous determination of salbutamol sulphate, bromhexine hydrochloride and etofylline in pharmaceutical formulations with the use of four rapid derivative spectrophotometric methods[J]. Anal. Chim. Acta, 2007, 597: 113–120.
[54] Lianidou E S, Ioannou P C, Polydorou C K, et al. Synchronous scanning second derivative spectrofluorimetry for the simultaneous determination of diflunisal and salicylic acid added to serum and urine as ternary complexes with terbium and EDTA[J]. Anal. Chim. Acta, 1996, 320: 107–114.
[55] Ruíz-Henestrosa V P, Sánchez C C, Rodríguez Patino J M. Adsorption and FoamingCharacteristics of Soy Globulins and Tween 20 Mixed Systems[J]. Ind. Eng. Chem. Res, 2008, 47: 2876–2885.
[56] Liu J, Xu G Y, Wu D, et al. Spectroscopic Study on the Interaction between Bovine Serum Albumin and Tween-20[J]. J. Dispers. Sci. Technol. 2006, 27: 835–838.
[57] Acharya K R, Bhattacharya S C, Moulik S P. The surfactant concentration-dependent behaviour of safranine T in Tween (20,40, 60, 80) and Triton X-100 micellar media[J]. J. Photochem. Photobiol. A: Chem, 1997, 109: 29–34.
[58] Cui H, Li S f, Lin X Q. Chemiluminescence of Ce(IV) and surfactant Tween 20[J]. Analyst, 2001, 126: 553–554.
[59] Khatua P K, Ghosh S K, Bhattacharya S C. Quenching of fluorescence of 3,7-diamino-2,8-dimethyl-5-phenyl phenazinium chloride by halides and pseudohalides in mixed micellar media[J]. J. Mol. Liq, 2006, 124: 45–50.
[60] Du B, Liu Y, Wei Q, et al. Catalytic Kinetic Spectrophotometric Determination of Trace Amounts of Copper (II) in Biosamples using Tween–20 Microemulsion as Sensitizer[J]. Anal. Lett, 2005, 38: 711–725.
[61] Al-Kindy S M Z, Suliman F O, Salama S B. A sequential injection method for the determination of aluminum in drinking water using fluorescence enhancement of the aluminum–morin complex in micellar media[J]. Microchem. J, 2003, 74: 173–179.
[62] Ouyang Y F, Wang Y S, Mi X W, et al. Resonance light scattering of 1-hydroxypyrene–ethyl-violet–anionic surfactant system and its analytical application[J]. Anal. Sci, 2007, 23: 533.
[63] Tang B, Wang X, Wang G, et al. Highly sensitive and selective spectrofluorimetric determination of tolnaftate through the formation of ternary inclusion complex ofβ-naphthol/-cyclodextrin/anionic surfactant system[J]. Talanta, 2006, 69: 113-120.
[64] Kim W H, Karim M M, Lee S H. Simultaneous determination of levodopa and carbidopa by synchronous fluorescence spectrometry using double scans[J]. Anal. Chim. Acta, 2008, 619: 2–7.
[65] Hua G X, Broderick J, Semple K T, et al. Rapid quantification of polycyclic aromatic hydrocarbons in hydroxypropyl-β-cyclodextrin (HPCD) soil extracts by synchronous fluorescence spectroscopy (SFS)[J]. Environ. Pollut, 2007, 148: 176–181.
[66] Wang S, Mulligan C N. Rhamnolipid biosurfactant-enhanced soil flushing for the removal of arsenic and heavy metals from mine tailings[J]. Process Biochem, 2009, 44: 296–301.
[67] Wang C C, Masi A N, Fernández L. On-line micellar-enhanced spectrofluorimetric determination of rhodamine dye in cosmetics[J]. Talanta, 2008, 75: 135–140.
[68] Guo C C, Wang L, Hou Z, et al. Micelle-enhanced and terbium-sensitized spectrofluorimetric determination of gatifloxacin and its interaction mechanism[J]. Spectrochim. Acta A, 2009, 72: 766–771.
[69] Sampera E, Rodrígueza M, De la Rubiab M A, et al. Removal of metal ions at low concentration by micellar-enhanced ultrafiltration (MEUF) using sodium dodecyl sulfate (SDS) and linear alkylbenzene sulfonate (LAS) [J]. Sep. Purif. Technol, 2009, 65: 337–342.
[70] Ruiz C C, Molina-Bolívar J A, Aguiar J, et al. Effect of ethylene glycol on the thermodynamic and micellar properties of Tween 20[J]. Colloid. Polym. Sci, 2003, 281: 531–541.
[71] Acharya K R, Bhattacharya S C, Moulik S P. Effects of urea and thiourea on the absorption and fluorescence behaviours of the dye safraninet in micellar medium[J]. J. Mol. Liq, 2000, 87: 85–96.
[72] Townshend A, Youngvises N, Wheatley R A, et al. Flow-injection determination of cinnarizine using surfactant-enhanced permanganate chemiluminesence[J]. Anal. Chim. Acta, 2003, 499: 223–233.
[73] IUPAC, in: J. Inczédy, T. Lengyel, A. M. Ure, A. Gelencsér, A. Hulanicki (Eds.), Compendium of Analytical Nomenclature, third ed., Blanckwell, Oxford, 1998, http://old.iupac.org/publications/analytical _compendium/.
[74]王英,王永生,曹晓娟,等.高效液相色谱–紫外检测法测定尿中α–萘酚、β–萘酚和1-羟基芘[J].中国卫生检验杂志, 2009, 19(3): 565–566.
[75]夏禹杰,曾建立,赵兵,等.反相高效液相色谱检测法测定溴化1-乙基-3-甲基咪唑–水体系中青蒿素[J].分析化学, 2009, 37(4): 573–576.
[76]陈硕,韩宗勋,全燮,等.毛细管固相微萃取液相色谱法测定水中的多环芳烃[J].分析化学, 2003, 31(2): 171–174.
[77]王春华,吴桂锋,杨平,等.多环芳烃不同程度污染城市人群尿中多环芳烃代谢产物水平的检测及其意义[J].吉林大学学报(医学版), 2010,36(1): 201–204.
[78]张川,毛静远,侯雅竹.代谢组学中数据采集及分析的研究进展[J].中国中西医结合杂志, 2009, 29(10): 949–952.
[1]杨发忠,颜阳,张泽志,等.多环芳烃研究进展[J].云南化工, 2005, 32(2): 45–48.
[2] Rey-Salueiro L, Martínez-Carballo E, García-Falcón M S, et al. Occurrence of polycyclic aromatic hydrocarbons and their hydroxylated metabolites in infant foods[J]. Food Chem, 2009, 115: 814–819.
[3] Orecchio S, Papuzza V. Levels, fingerprint and daily intake of polycyclic aromatic hydrocarbons (PAHs) in bread baked using wood as fuel[J]. J. Hazard. Mater, 2009, 164: 876–883.
[4] Sang L Z, Wei X Y, Chen J N, et al. Simultaneous fluorimetric determination of the biodegradation processes of dissolved multi-component PAHs[J]. Talanta, 2009, 78: 1339–1344.
[5] Jongeneelen F J, Anzion R B M, Henderson P T. Determination of hydroxylated metabolites of polycyclic aromatic hydrocarbons in urine[J]. J. Chromatogr, 1987, 413: 227–232.
[6] Jongeneelen F J. Benchmark guideline for urinary 1-hydroxypyrene as biomarker of occupational exposure to polycyclic aromatic hydrocarbons[J]. Ann. Occup. Hyg, 2001, 45(1): 3–13.
[7] Jacob J, Seidel A. Biomonitoring of polycyclic aromatic hydrocarbons in human urine[J]. J. Chromatogr. B, 2002, 778: 31–47.
[8] Hansen ? M, Mathiesen L, Pedersen M, et al. Urinary 1-hydroxypyrene (1-HP) in environmental and occupational studies—A review[J]. Int. J. Hyg. Environ. Health, 2008, 211: 471–503.
[9] Li Z, Sandau C D, Romanoffa L C, et al. Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population[J]. Environ. Res, 2008, 107: 320–331.
[10]万红丽,周光宏,徐幸莲,等.肉制品中多环芳烃前处理技术的研究进展[J].食品研究与开发, 2006, 27(8): 124–126.
[11]贾瑞宝,孙韶华,刘德珍.用固相萃取技术富集水中多环芳烃[J].色谱, 1997, 15 (6): 524–526.
[12]周晓珍.固相萃取技术富集水中的多环芳烃[J].江西化工, 2006, 2: 48–49.
[13]何燕,冯琳.多环芳烃的样品前处理技术研究进展[J].重庆师范大学学报(自然科学版), 2007, 24(3): 64–68.
[14]刘桂明,邓义敏.二极管阵列检测器和荧光检测器联合测定饮用水中多环芳烃[J].中国卫生检验杂志, 2007, 17(11): 1943–1946.
[15]郁建栓,朱晨红.高效液相色谱荧光检测快速分析水中多环芳烃化合物[J].中国环境监测, 1997, 13(1): 20–22.
[16]石璐.环境水样中痕量多环芳烃的分析研究进展[J].企业技术开发, 2007, 26(10): 7–10.
[17]贾瑞宝.水中痕量多环芳烃(PAHs)类环境污染物检测方法的研究[J].中国环境监测[J]. 1999, 15(1): 40–42.
[18]饶竹,李松.何淼苏劲高效液相色谱–荧光–紫外串联测定土壤中16种多环芳烃[J].分析化学研究报告, 2007, 35(7): 954–958.
[19]钱薇,倪进治,骆永明,等.高效液相色谱–荧光检测法测定土壤中的多环芳烃[J].色谱, 2007, 25(2): 221–225.
[20]胡健,张国平,刘丛强.固相萃取柱净化–液相色谱法测定大气中多环芳烃地球与环境, 2004, 32(3-4): 94–97.
[21]闫小华,张毕奎,李焕德,等.紫外检测器–荧光检测器串联的HPLC法测定火力发电厂环境中的多环芳烃[J].色谱, 2000, 18(5): 432–435.
[22]刘颖,陈玲,唐银健,等.高效液相色谱法测定黄浦江表层沉积物中的痕量多环芳烃[J].色谱, 2007, 25(3): 356–361.
[23]张德云,孙成均,王涛.高效液相色谱法测定室内空气中13种多环芳烃[J].华西医大学报, 2002, 33 (1): 140–143.
[24]廖倩,高振江,张世湘,等.高效液相荧光法测定“北京烤鸭”鸭皮中的多环芳烃[J].食品科学, 2009, 30(10): 149–152.
[25]张峻松,戴勇,贾春晓,等.卷烟主流烟气中苯并[a]芘的HPLC测定[J].烟草科技/烟草化学, 2003, 4: 22–24.
[26]樊虎,盛良全,童红武,等.固相萃取-高效液相色谱法测定卷烟主流烟气中的多环芳烃[J].分析测试学报, 2005, 24(1): 103–105.
[27]林玉,李怿,白正伟,等.高效液相色谱–光电二极管阵列检测法测定柴油中芳烃的类型[J].色谱, 2008, 26(2): 250–253.
[28] Elovaara E, Vaananen V, Mikkola J. Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intrainadividual variance in the urinary metabolite excretion profiles caused by intervention withβ-naphthoflavone induction in the rat[J]. Arch Toxicol, 2003, 77: 183–193.
[29] Hollender J, Koch B, Dott W. Biomonitoring of environmental polycyclic aromatic hydrocarbon exposure by simultaneous measurement of urinary phenanthrene, pyrene and benzo[a]pyrene hydroxides[J]. J. Chromatogr. B, 2000, 739: 225–229.
[30]李晓华,冷曙光,郭君,等.改良的高效液相色谱法测定尿中1-羟基芘[J].卫生研究, 2003, 32(6): 616–617.
[31]王宇,董玉莲,范瑞芳,等.尿中多种多环芳烃代谢物同时测定的高效液相色谱-荧光检测法[J].环境与健康杂志, 2006, 23(1): 76–78.
[32]肖海清,王星,王超,等.气相色谱–质谱法测定塑料制品中多环芳烃[J].理化检验-化学分册, 2009, 45(2): 187–190.
[33]杨家锋,钟惠英,段青源,等.气相色谱–质谱联用法测定水产品中16种多环芳烃[J].中国卫生检验杂志, 2009, 19(10): 2291–2295.
[34]姜晓黎,梁鸣,翁若荣,等.气相色谱–质谱法测定电子电气产品材料中多环芳烃[J].福建分析测试, 2009, 18(2): 50–54.
[35]常薇,郁翠华,周娟.单液滴微萃取–气相色谱/质谱法检测水中多环芳烃[J].环境污染与防治, 2009, 31(5): 54–57.
[36]王楼明,李英,杨左军,等. GC/MS法测定润滑油基础油中多环芳烃[J].环境污染与防治, 2009, 31(2): 67–73.
[37]王志,李洁,李振国.加速溶剂萃取凝胶色谱净化气相色谱–质谱联用测定土壤中多环芳烃[J].光谱实验室, 2009, 26(4): 831–834.
[38] Grainger J, Huang W L, Patterson Jr D G, et al. Reference range levels of polycyclic aromatic hydrocarbons in the US population by measurement of urinary monohydroxy metabolites[J]. Environ. Res, 2006, 100: 394–423.
[39] Luan T G, Fang S H, Zhong Y, et al. Determination of hydroxy metabolites ofpolycyclic aromatic hydrocarbons by fully automated solid-phase microextraction derivatization and gas chromatography–mass spectrometry[J]. J. Chromatogr. A, 2007, 1173: 37–43.
[40] Romanoff L C, Li Z, Young K J, et al. Automated solid-phase extraction method for measuring urinary polycyclic aromatic hydrocarbon metabolites in human biomonitoring using isotope-dilution gas chromatography high-resolution mass spectrometry[J]. J. Chromatogr. B, 2006, 835: 47–54.
[41] Grosse S, Letzel T. Liquid chromatography/atmospheric pressure ionization mass spectrometry with post-column liquid mixing for the efficient determination of partially oxidized polycyclic aromatic hydrocarbons[J]. J. Chromatogr. A, 2007, 1139: 75–83.
[42] Delhommea O, Millet M, Herckes P. Determination of oxygenated polycyclic aromatic hydrocarbons in atmospheric aerosol samples by liquid chromatography– tandem mass spectrometry[J]. Talanta, 2008, 74: 703–710.
[43]何立芳,林丹丽,李耀群.多环芳烃混合物的快速导数-恒能量同步荧光光谱分析[J].应用化学, 2004, 21(9): 937–943.
[44]蔡其洪.恒波长同步荧光法同时测定三种多环芳烃[J].莆田学院学报, 2006, 13(5): 80–83.
[45]李静红,于连生,杜尧国,等.二阶导数同步荧光光谱法测定大气飘尘中苯并(a)芘[J].东北电力学院学报, 1995, 15(3): 91–94.
[46]於立军,李耀群,眭蔚.多环芳烃的Shpol′skii低温荧光光谱分析[J].光谱学与光谱分析, 2002, 22(15): 819–821.
[47] De Alda Villaizán M J L, García Falcón M S, González Amigo S, et al. Second-derivative constant-wavelength synchronous scan spectrofluorimetry for determination of benzo[b]fluoranthene, benzo[a]pyrene and indeno[1,2,3-cd]pyrene in drinking water[J]. Talanta, 1996, 43: 1405–1411.
[48]鄢远,王乐天,许金钩.三维导数荧光光谱总体积积分法同时测定多环芳烃[J].化学学报, 1996, 24(9): 772–776.
[49] Yang H M, Wang Y S, Li J H, et al. Synchronous fluorescence determination of urinary 1-hydroxypyrene, 1-naphthol and 9-hydroxyphenanthrene based on the sensitizingeffect ofβ-cyclodextrin[J]. Anal. Chim. Acta, 2009, 636: 51–57.
[50]杨欣,晋卫军,魏雁声,等.导数–化学除氧微乳状液增稳室温磷光法同时测定痕量荧蒽与苊的研究[J].西南师范大学学报(自然科学版), 1994, 19(增刊): 116–117.
[51]杨欣,董川,魏雁声,等.同步扫描–微乳状液增稳室温磷光法同时测定痕量多环芳烃的研究[J].高等学校化学学报, 1996, 17(5): 716–718.
[52]晋卫军,董川,魏雁声,等.室温磷光:方法、机理和应用[J].福州大学学报(自然科学版), 1999, 27(增刊): 15–16.
[53]李隆弟,牟兰,陈小康.多环芳烃芴、苊的无保护流体室温磷光性质[J].研究高等学校化学学报, 2000, 21(7): 1040–1043.
[54] Li K, Woodward L A, Karu A E, et al. Immunochemical detection of polycyclic aromatic hyxrocarbons and 1-hydroxypyrene in water and sediment samples[J]. Anal. Chim. Acta, 2000, 419: 1–8.