毛细管电泳环境污染物微分析技术的应用
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摘要
论文运用毛细管电泳紫外检测技术，采用直接紫外检测、间接紫外检测和络合衍生紫外检测技术等，针对环境污染物种类不同，建立了适应对环境中重金属污染物、阴离子污染物、海洋生物污染物的毛细管电泳检测方法。
全文共分为5部分。第1章概要介绍了毛细管电泳技术的兴起与发展，对毛细管电泳的基本原理进行了简要概述。第2章阐述了环境中的无机污染物和毛细管电泳的关系，包括检测无机污染物常用的方法和毛细管电泳检测无机离子技术。第3章主要是针对海洋生物污染物-贝类毒素的分析，介绍了贝类毒素的产生机制、机理和对人体的毒害，围绕5种常见贝毒(腹泻性贝毒、麻痹性贝毒、记忆缺损性贝毒、神经性贝毒和西加鱼毒素)，分别介绍了其物理化学性质、毒理与毒性、在中国和世界各地的分布状况以及目前经常采用的分析方法。
第4章是论文的核心部分，包括5项实验内容：(1)直接检测水中重金属污染物Fe~(3+)和Cu~(2+)的方法、(2)间接紫外检测金属离子，测定水体中活泼金属阳离子Na~-、Mg~(2+)和Ca~(2+)等、(3)将间接紫外技术进一步应用于自来水中SO_4~(2-)等阴离子检测、(4)研究了络合衍生紫外技术，对四种重金属污染物Cu~(2+)、Fe(3+)、Mn~(2+)、Zn~(2+)进行了检测，取得了良好的重现性及检测限、(5)针对海洋生物污染物贝毒的检测，建立了毛细管电泳分析技术，对南海、东海和北部海域等53个不同地区的69个贝类样品考查，并以遗忘性贝毒为样本，进行了毛细管电泳检验和质谱验证，研究发现，中国北方海域广泛含有遗忘性贝毒。
在最后一章里，归类和总结了毛细管电泳应用过程中的技术问题。
The capillary electrophoresis (CE) technique is applied in the thesis. According to different types of environmental pollutant, we set up direct UV detection, indirect UV detection and UV-derived detection methods to analyze a series of environmental pollutants such as metal ion pollutant, anion pollutant and marine pollutant.
This thesis contains 5 chapters. The first one gives a general introduction of the capillary electrophoresis, and the 2nd chapter investigates the ion pollutant relevant to CE. The 3rd chapter introduces the sea shellfish toxin, which is a typical sea pollutant, then, it classifies some well known shellfish poisons, including DSP, PSP, ASP. NSP and Ciguatera. Finally it introduces their characteristics, poisoning and the distribution respectively, and summarized biochemistry and instrumental analysis methods.
The core of the thesis is the 4the one, which contained 5 parts. Firstly, it introduces the analyses of the Cu2+ and Fe3+ carried by direct UV detection, secondly, it introduces the method to measure several cations of Ca2+, Na+, Mg2+ in the tap water. And the 3rd part is about the detection of SO42- in the tap water using indirect UV technique. The 4th part introduces the method to detect Cu2+, Fe3+, Mn2+, Zn2+. The following part concerns about natural organic pollutant as well as its analytical method using CE. Choosing DA(domoic acid) as candidate analyte, we obtained 69 shellfish samples from 53 sites dispersed along seacoast of China (South China Sea, East China Sea and North China Sea). DA was examined not only by CE but also by mass spectra (MS). The result shows that DA was found in shellfishes variously in North China Sea but not found in other areas.
Finally, we classified the technological questions while using CE.
全文共分为5部分。第1章概要介绍了毛细管电泳技术的兴起与发展，对毛细管电泳的基本原理进行了简要概述。第2章阐述了环境中的无机污染物和毛细管电泳的关系，包括检测无机污染物常用的方法和毛细管电泳检测无机离子技术。第3章主要是针对海洋生物污染物-贝类毒素的分析，介绍了贝类毒素的产生机制、机理和对人体的毒害，围绕5种常见贝毒(腹泻性贝毒、麻痹性贝毒、记忆缺损性贝毒、神经性贝毒和西加鱼毒素)，分别介绍了其物理化学性质、毒理与毒性、在中国和世界各地的分布状况以及目前经常采用的分析方法。
第4章是论文的核心部分，包括5项实验内容：(1)直接检测水中重金属污染物Fe~(3+)和Cu~(2+)的方法、(2)间接紫外检测金属离子，测定水体中活泼金属阳离子Na~-、Mg~(2+)和Ca~(2+)等、(3)将间接紫外技术进一步应用于自来水中SO_4~(2-)等阴离子检测、(4)研究了络合衍生紫外技术，对四种重金属污染物Cu~(2+)、Fe(3+)、Mn~(2+)、Zn~(2+)进行了检测，取得了良好的重现性及检测限、(5)针对海洋生物污染物贝毒的检测，建立了毛细管电泳分析技术，对南海、东海和北部海域等53个不同地区的69个贝类样品考查，并以遗忘性贝毒为样本，进行了毛细管电泳检验和质谱验证，研究发现，中国北方海域广泛含有遗忘性贝毒。
在最后一章里，归类和总结了毛细管电泳应用过程中的技术问题。
The capillary electrophoresis (CE) technique is applied in the thesis. According to different types of environmental pollutant, we set up direct UV detection, indirect UV detection and UV-derived detection methods to analyze a series of environmental pollutants such as metal ion pollutant, anion pollutant and marine pollutant.
This thesis contains 5 chapters. The first one gives a general introduction of the capillary electrophoresis, and the 2nd chapter investigates the ion pollutant relevant to CE. The 3rd chapter introduces the sea shellfish toxin, which is a typical sea pollutant, then, it classifies some well known shellfish poisons, including DSP, PSP, ASP. NSP and Ciguatera. Finally it introduces their characteristics, poisoning and the distribution respectively, and summarized biochemistry and instrumental analysis methods.
The core of the thesis is the 4the one, which contained 5 parts. Firstly, it introduces the analyses of the Cu2+ and Fe3+ carried by direct UV detection, secondly, it introduces the method to measure several cations of Ca2+, Na+, Mg2+ in the tap water. And the 3rd part is about the detection of SO42- in the tap water using indirect UV technique. The 4th part introduces the method to detect Cu2+, Fe3+, Mn2+, Zn2+. The following part concerns about natural organic pollutant as well as its analytical method using CE. Choosing DA(domoic acid) as candidate analyte, we obtained 69 shellfish samples from 53 sites dispersed along seacoast of China (South China Sea, East China Sea and North China Sea). DA was examined not only by CE but also by mass spectra (MS). The result shows that DA was found in shellfishes variously in North China Sea but not found in other areas.
Finally, we classified the technological questions while using CE.
引文
[1] P. B. Wright, A. S. Lister, J. O. Dorsey, Anal, Chem., 1997, 69, 3251～3269
[2] Stwinbrech B. Speciation of arsenicand chromiummetal ions by reversed phase high performance liquid Chromatog-raphy. Journal of Liquid Chromatography, 1987, 10(1): 1～15
[3] 程介克，高效液相色谱分光光度测定痕量金属．高等学校化学学报，1995，16(5)：696～699
[4] 杨丙雨，李智民，杂环偶氮试剂在金属高效液相色谱．光度法中的应用，冶金分析，1996，16(4)：30～35．
[5] 石志红，傅承光，卟啉在高效液相色谱．光度法测定痕量金属离子方面的应用，分析测试技术与仪器，1996，2(3)：28～33
[6] SaitonK, SuzukiN. Chromatographic determination of metallic impurities inreversed-phase HPLC columns.Ana-lyticalChemistry, 1991,63:2309.
[7] 施红林等 高效液相色谱法测定烟草中的铁、钴、镍、铜、锌、锰中国烟草学报，2003，5～7
[8] 任一平，陈青俊，黄百芬．高效毛细管电泳法测定饮用水中的无机阴离子[A]．毛细管电泳进展(二)[C]．1995，164～165．
[9] 刘嘉松，孙建英．毛细管电泳技术用于分析水中常见的阳离子[A]．毛细管电泳进展(二)[C]．1995，150～152．
[10] 万涛，王勇，本水昌山．天然水中钙、镁离子的测定[J]．广东微量元素科学．1999，6(8)：61～63．
[11] 杨永坛，康经武，李菊白，等．高效毛细管电泳测定混合氯化稀土中的稀土元素[J]．分析测试技术与仪器．1997，3(2)：80～85．
[12] Wen J, Baranskia, Cassicyr. Cyclic Voltammetric Detection in Capillary Electrophoresis with Application to Metal Ions [J]. Analchem. 1998, 70(13): 2504～2509.
[13] 杨捷，陈国平，吴晓萍．毛细管电泳分离测定金属阳离子[J]．矿产与地质．2000，14(2)：127～129．
[14] Wright, J. L. C., Boyd, R. K., Defreitas, A. S. W., Falk, M., et al., Can. J. Chem 1989, 67, 481—490.
[15] Soames Marci CP. Shellfish poisoning. Chem in Aust, 1995:62(2):22
[16] Tasumoto T. Oshima M. Y. and Yamaguchi, M. Occurrence of a new type of shellfish poisoning in the Tohoku District. Bull Jpn. Soc. Sci. Fish, 44(1978) 1249～1255
[17] 中国有害赤潮信息网 http://www.china-hab.ac.cn
[18] Dickey R W and Bencsath F A. A comparison of methods for the HPLC fluorometric analysis of okadaic acid. In Third Int. Cong. on Ciguatera Fish Poisoning. Puerto Rico. April 30-May 4, 1990, Abst: 6～7
[19] Akasaka A, et, al. Fluorimetic determination of diarrhetic shellfish toxins in scallops and mussels by high-performance liquid chromatography. J. Chromatogr. 1996; 729(1): 381～389
[20] Shen J, et al. Sensitive HPLC-Fluorometric and HPLC-MS determination of diarrhetic shellfish poisoning (DSP) toxins as 4-bromomethyl-7-meth oxycou marinesters. Fresenius J. Anal. Chem. 1997; 357～361
[21] Jose C. Gonzalexz, et. Improvement on sample clean-up for high-performance liquid chromatographic fluorimetric determination of diarrhetic shellfish toxins using 1-bromoacetylpyrene journal of Chromatography A 793 (1998)63～70
[22] Lee J S. Yanagi T. Kanna R., Yasumoto T. Fluorometric determination of diarrhetic shellfish toxins by high performance liuid chromatography. Agric Biol Chem, 1987, 51: 877～885
[23] Qshima Y. Post-coluumn derivatization liquid chromatographic method fro paralytic shellfish toxins. JAOAC 1995; 78(2):528～529
[24] Lawrence JF, et al. Development of a manganese dioxide solide-phase reactor for oxidation of toxins associated with paralytic shellfish poisoning. J. Chromatorgr, 1996; 755: 227～232
[25] James FL, et al. Evaluation of a postcolumn electrochemical reactor for oxidation of paralytic shellfish poison toxins. JAOAC, 1995; 78 (3): 698～704
[26] Lawrence JF, et al. Evaluation of pre-chromatographic oxidation for liquid chromatorgraphic determination of paralytic shellfish. JAOAC 1995; 78(2): 514～518
[27] Clin JD, et al. Screening for okadaic acid by immunoassay. JAOAC 1995, 78(2):508～510
[28] Hua, Y. S. and Cole, R. B. 'Electrospray lonixation Tandem Mass Spectrometry for Structural Elucidation of Protonated brevetoxins in Red Tide Algae' in Analytical chemistry 2000, 72, 376～383.
[29] Yasumoto T. et al. Determinations of marine toxins in foods. JAOAC 1995: 78(2):574～578
[30] Hallegraeff G M. Manual on HarmfuL Marine micro-algae UNESCO, France: IOC Manuals and Guides NO. 33.1995.182～199
[31] Garthwaite, I., Ross, K. M. and Haywood, A. Detection of NSP (Brevetoxins) in Algal CuLtures and Seawater by ELISA in Proceedings of the 10th Bio-toxin Science Workshop, MAS New Xealand, Washington, 1998, 51～54,
[32] Soams Mraci CP. Shellfish poisoning, Chem. in Aust. 1995: 62(2):22～24
[33] Jellett, Joanne F, Marks Linda J. Stewart James E. et al. Paralytic Shellfish poison (Saxitoxin family) biassays: automated endpoint determination and standardization of the in vitro tissue ecuLture bioassay, and comprison with the standard mouse bioassay. Toxion, 1992, 30(10):1143～1156
[34] 陈杰，曹雅明等 细胞毒性试验测定麻痹性贝毒的检测方法 中国公共卫生 2001，17(11)：994～998
[35] TsudaT, Noura K, Nakagawa G. J. Chromatogr. 1983, 264: 385
[36] Ding Yongsheng, Xue Jun and Lin Bingcheng.Application of capillary electrophoresis on environmental analysis (J),Chromatography, 1998,16(3):215～219
[37] Yang Yongtan, Seperation and Determination of Trace Cations from Snow Sample by Capillary Electrophoresis With Sample Stacking mol/Lode, Chinese Journal of Analytical Chemistry, 1999, 433～436
[38] 林炳承，毛细管电泳导论[M]．北京：科学出版社，1996，21～159
[39] 丁永生，薛俊，林炳承，毛细管电泳在环境分析中的运用[J]．色谱 1998，16(3)：215～217
[40] Hossein S M, Cassidy R'M, Control of Separation Selectivity and Electroosmotic Flow in Nonaqueous capillary Electrophoretic Separation of Alkali and Alkaline Earth Metal Ions [J]. J Chromatogr. A. 1996. 749: 279～286
[41] 陈义，毛细管电泳技术及应用，北京化学工业出版社，2000，213～241
[42] N.Iki, H. Hoshino, T. Yotsuyanagi, J. Chromatogr., 1993, 539～652
[43] Wright, J. L. C., Boyd, R. K., Defreitas, A. S. W., Falk, M., et al., Can. J. Chem 1989, 67, 481～490.
[44] Todd, E., a review. J. Food Protect. 1993, 56 (1), 69～83.
[45] Bates, S. S., J. Phycol. 2000, 36, 978～985.
[46] Teitelbaum, J. S., Zatorre, R. J., Carpenter, S., Gendron, D., Evans, A. C., Gjedde, A., Cashman, N. R., New England Journal of Medicine 1990, 322, 1781～1787.
[47] Lizzy, M., Environmental Toxicology and Pharmacology 2001, 9, 79～85.
[48] Bates, S. S., Bird, C. J., de Freitas, A. S M. W., Hanic, L. A., et al., Can., J. Fish. Aquat. Sci. 1989, 46, 1203～1215.
[49] Rue, E., Bruland, K., Marine Chemistry 2001, 76, 127～134.
[50] Horner, R. A., Garrison, D. L., Plumley, F. G., WestCoast. Limnol. Oceanogr. 1997, 42, 1076～1088.
[51] Kotaki, Y., Koike, K., Ogata, T., Sato, S., et al., Harmful and Toxic Algal Blooms IOC～UNESCO, Paris 1996, 151～153.
[52] Rhods L., White, D., Syhre, M., Atkinson, M., In: Yasumoto, T., Oshima, Y, Fukuyo, Y. (eds.) Harmful andToxic Algal Blooms, Intergov. Oceanogr. Comm., UNESCO, Paris, 1996, 155～158.
[53] Miguez, (?)., Fern(?)ndez, M. L., Fraga, S., In: Yasumoto, T., et al., Harmful and Toxic Algal Blooms IOC UNESCO, 1996, 143～145.
[54] Vale, P., Sampayo, M. A., Quilliam, M. A., Harmful Algae Xunta de Galicia and Intergovemmental Oceanographic Commission of UNESCO, Vigo, Spain, 1998,503～506.
[55] Bates, S. S., Garrison, D. L., Horner, R. A., Physiological Ecology of Harmful Algal Blooms Springe-Verlag, Heidelberg. 1998, 267～292.
[56] Zouh er, A., Jaqueline, F., Dominique, L. G., Chantal, B., Toxicon 2001, 39, 1245～1251.
[57] Zhou, M. J., Li, J., Luckas, B., Yu, R. C., et al., Marine Pollution Bulletin 1999, 39, 331～334.
[2] Stwinbrech B. Speciation of arsenicand chromiummetal ions by reversed phase high performance liquid Chromatog-raphy. Journal of Liquid Chromatography, 1987, 10(1): 1～15
[3] 程介克，高效液相色谱分光光度测定痕量金属．高等学校化学学报，1995，16(5)：696～699
[4] 杨丙雨，李智民，杂环偶氮试剂在金属高效液相色谱．光度法中的应用，冶金分析，1996，16(4)：30～35．
[5] 石志红，傅承光，卟啉在高效液相色谱．光度法测定痕量金属离子方面的应用，分析测试技术与仪器，1996，2(3)：28～33
[6] SaitonK, SuzukiN. Chromatographic determination of metallic impurities inreversed-phase HPLC columns.Ana-lyticalChemistry, 1991,63:2309.
[7] 施红林等 高效液相色谱法测定烟草中的铁、钴、镍、铜、锌、锰中国烟草学报，2003，5～7
[8] 任一平，陈青俊，黄百芬．高效毛细管电泳法测定饮用水中的无机阴离子[A]．毛细管电泳进展(二)[C]．1995，164～165．
[9] 刘嘉松，孙建英．毛细管电泳技术用于分析水中常见的阳离子[A]．毛细管电泳进展(二)[C]．1995，150～152．
[10] 万涛，王勇，本水昌山．天然水中钙、镁离子的测定[J]．广东微量元素科学．1999，6(8)：61～63．
[11] 杨永坛，康经武，李菊白，等．高效毛细管电泳测定混合氯化稀土中的稀土元素[J]．分析测试技术与仪器．1997，3(2)：80～85．
[12] Wen J, Baranskia, Cassicyr. Cyclic Voltammetric Detection in Capillary Electrophoresis with Application to Metal Ions [J]. Analchem. 1998, 70(13): 2504～2509.
[13] 杨捷，陈国平，吴晓萍．毛细管电泳分离测定金属阳离子[J]．矿产与地质．2000，14(2)：127～129．
[14] Wright, J. L. C., Boyd, R. K., Defreitas, A. S. W., Falk, M., et al., Can. J. Chem 1989, 67, 481—490.
[15] Soames Marci CP. Shellfish poisoning. Chem in Aust, 1995:62(2):22
[16] Tasumoto T. Oshima M. Y. and Yamaguchi, M. Occurrence of a new type of shellfish poisoning in the Tohoku District. Bull Jpn. Soc. Sci. Fish, 44(1978) 1249～1255
[17] 中国有害赤潮信息网 http://www.china-hab.ac.cn
[18] Dickey R W and Bencsath F A. A comparison of methods for the HPLC fluorometric analysis of okadaic acid. In Third Int. Cong. on Ciguatera Fish Poisoning. Puerto Rico. April 30-May 4, 1990, Abst: 6～7
[19] Akasaka A, et, al. Fluorimetic determination of diarrhetic shellfish toxins in scallops and mussels by high-performance liquid chromatography. J. Chromatogr. 1996; 729(1): 381～389
[20] Shen J, et al. Sensitive HPLC-Fluorometric and HPLC-MS determination of diarrhetic shellfish poisoning (DSP) toxins as 4-bromomethyl-7-meth oxycou marinesters. Fresenius J. Anal. Chem. 1997; 357～361
[21] Jose C. Gonzalexz, et. Improvement on sample clean-up for high-performance liquid chromatographic fluorimetric determination of diarrhetic shellfish toxins using 1-bromoacetylpyrene journal of Chromatography A 793 (1998)63～70
[22] Lee J S. Yanagi T. Kanna R., Yasumoto T. Fluorometric determination of diarrhetic shellfish toxins by high performance liuid chromatography. Agric Biol Chem, 1987, 51: 877～885
[23] Qshima Y. Post-coluumn derivatization liquid chromatographic method fro paralytic shellfish toxins. JAOAC 1995; 78(2):528～529
[24] Lawrence JF, et al. Development of a manganese dioxide solide-phase reactor for oxidation of toxins associated with paralytic shellfish poisoning. J. Chromatorgr, 1996; 755: 227～232
[25] James FL, et al. Evaluation of a postcolumn electrochemical reactor for oxidation of paralytic shellfish poison toxins. JAOAC, 1995; 78 (3): 698～704
[26] Lawrence JF, et al. Evaluation of pre-chromatographic oxidation for liquid chromatorgraphic determination of paralytic shellfish. JAOAC 1995; 78(2): 514～518
[27] Clin JD, et al. Screening for okadaic acid by immunoassay. JAOAC 1995, 78(2):508～510
[28] Hua, Y. S. and Cole, R. B. 'Electrospray lonixation Tandem Mass Spectrometry for Structural Elucidation of Protonated brevetoxins in Red Tide Algae' in Analytical chemistry 2000, 72, 376～383.
[29] Yasumoto T. et al. Determinations of marine toxins in foods. JAOAC 1995: 78(2):574～578
[30] Hallegraeff G M. Manual on HarmfuL Marine micro-algae UNESCO, France: IOC Manuals and Guides NO. 33.1995.182～199
[31] Garthwaite, I., Ross, K. M. and Haywood, A. Detection of NSP (Brevetoxins) in Algal CuLtures and Seawater by ELISA in Proceedings of the 10th Bio-toxin Science Workshop, MAS New Xealand, Washington, 1998, 51～54,
[32] Soams Mraci CP. Shellfish poisoning, Chem. in Aust. 1995: 62(2):22～24
[33] Jellett, Joanne F, Marks Linda J. Stewart James E. et al. Paralytic Shellfish poison (Saxitoxin family) biassays: automated endpoint determination and standardization of the in vitro tissue ecuLture bioassay, and comprison with the standard mouse bioassay. Toxion, 1992, 30(10):1143～1156
[34] 陈杰，曹雅明等 细胞毒性试验测定麻痹性贝毒的检测方法 中国公共卫生 2001，17(11)：994～998
[35] TsudaT, Noura K, Nakagawa G. J. Chromatogr. 1983, 264: 385
[36] Ding Yongsheng, Xue Jun and Lin Bingcheng.Application of capillary electrophoresis on environmental analysis (J),Chromatography, 1998,16(3):215～219
[37] Yang Yongtan, Seperation and Determination of Trace Cations from Snow Sample by Capillary Electrophoresis With Sample Stacking mol/Lode, Chinese Journal of Analytical Chemistry, 1999, 433～436
[38] 林炳承，毛细管电泳导论[M]．北京：科学出版社，1996，21～159
[39] 丁永生，薛俊，林炳承，毛细管电泳在环境分析中的运用[J]．色谱 1998，16(3)：215～217
[40] Hossein S M, Cassidy R'M, Control of Separation Selectivity and Electroosmotic Flow in Nonaqueous capillary Electrophoretic Separation of Alkali and Alkaline Earth Metal Ions [J]. J Chromatogr. A. 1996. 749: 279～286
[41] 陈义，毛细管电泳技术及应用，北京化学工业出版社，2000，213～241
[42] N.Iki, H. Hoshino, T. Yotsuyanagi, J. Chromatogr., 1993, 539～652
[43] Wright, J. L. C., Boyd, R. K., Defreitas, A. S. W., Falk, M., et al., Can. J. Chem 1989, 67, 481～490.
[44] Todd, E., a review. J. Food Protect. 1993, 56 (1), 69～83.
[45] Bates, S. S., J. Phycol. 2000, 36, 978～985.
[46] Teitelbaum, J. S., Zatorre, R. J., Carpenter, S., Gendron, D., Evans, A. C., Gjedde, A., Cashman, N. R., New England Journal of Medicine 1990, 322, 1781～1787.
[47] Lizzy, M., Environmental Toxicology and Pharmacology 2001, 9, 79～85.
[48] Bates, S. S., Bird, C. J., de Freitas, A. S M. W., Hanic, L. A., et al., Can., J. Fish. Aquat. Sci. 1989, 46, 1203～1215.
[49] Rue, E., Bruland, K., Marine Chemistry 2001, 76, 127～134.
[50] Horner, R. A., Garrison, D. L., Plumley, F. G., WestCoast. Limnol. Oceanogr. 1997, 42, 1076～1088.
[51] Kotaki, Y., Koike, K., Ogata, T., Sato, S., et al., Harmful and Toxic Algal Blooms IOC～UNESCO, Paris 1996, 151～153.
[52] Rhods L., White, D., Syhre, M., Atkinson, M., In: Yasumoto, T., Oshima, Y, Fukuyo, Y. (eds.) Harmful andToxic Algal Blooms, Intergov. Oceanogr. Comm., UNESCO, Paris, 1996, 155～158.
[53] Miguez, (?)., Fern(?)ndez, M. L., Fraga, S., In: Yasumoto, T., et al., Harmful and Toxic Algal Blooms IOC UNESCO, 1996, 143～145.
[54] Vale, P., Sampayo, M. A., Quilliam, M. A., Harmful Algae Xunta de Galicia and Intergovemmental Oceanographic Commission of UNESCO, Vigo, Spain, 1998,503～506.
[55] Bates, S. S., Garrison, D. L., Horner, R. A., Physiological Ecology of Harmful Algal Blooms Springe-Verlag, Heidelberg. 1998, 267～292.
[56] Zouh er, A., Jaqueline, F., Dominique, L. G., Chantal, B., Toxicon 2001, 39, 1245～1251.
[57] Zhou, M. J., Li, J., Luckas, B., Yu, R. C., et al., Marine Pollution Bulletin 1999, 39, 331～334.