磺酸化聚合环糊精的制备及评价
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摘要
近年来,对映异构体的分离成为药物分析中非常重要的研究领域。毛细管电泳在电渗流驱动下形成塞流,试剂、样品消耗少。在毛细管电泳中进行手性分离可以采取在毛细管电泳的背景缓冲液中添加具有手性识别能力的选择剂,或者将手性固定相键合在毛细管内壁,此时毛细管电泳分别采取区带电泳和电色谱的形式。电色谱兼具毛细管电迁移的高效和色谱的选择性,成为近年来对映体分离的热点。环糊精及其衍生物是最为常用的一类手性选择剂,其中磺酸化环糊精应用和研究最为广泛,它具有水溶性好,手性识别能力强,可分离的手性化合物范围广等优点。但是,磺酸化环糊精作为选择剂使用时,要求它结构均一,纯度高,所以反应步骤繁琐,售价非常昂贵。
为了解决定位反应的磺酸化环糊精以上不足,本文在大量研究的基础上,设计了含有硅氧键的磺酸化β—环糊精这一分子结构,从统计学和高分子的角度,获得了在电泳中均一化的环糊精。并可以通过硅氧键与毛细管壁键合。所得到产品同样可以获得较好的水溶性。通过对比产品作为手性添加剂和手性固定相在不同pH条件下对电渗流的抑制作用,考察了其电泳行为。在电色谱形式下对电渗流的抑制作用非常明显；作为添加剂时在整个考察pH区间内,电渗流变化平缓。在不同pH值条件下考察pH环境分别对几种代表性手性药物的分离作用,结果显示有的获得了手性分离效果,有的两种对映体在出峰时间上有明显区别。对比其不同作用方式的作用结果,分别对不同药物具有手性分离能力,说明其在不同电泳模式下的作用能力、结合方式有很大差别。
利用实验室己建立的电喷雾制备纳米硅球技术,制备带有手性分离基团的纳米级微球。并将其作为手性添加剂考察对电渗流的抑制作用。对手性药物进行分离的过程中对所有的酸性药物无法分离。而对华法令的分离有拖尾现象,说明微球上确实键合上对手性药物具有分离能力的官能团,但其作用能力还非常有限。因此,在制球过程中如何提高硅烷偶联剂与产品的结合能力是制备中的关键技术。
In recent years, the separation of enantiomers is of primary importance in pharmaceutical analysis. The main advantage of electromigration techniques is the high efficiency due to the plug-like flow profile caused by the EOF. Furthermore, there is a low solvent and selector consumption. Chiral CE separations of drugs have two major modes:chiral selector is added in buffer as chiral additive, or chiral selector is reacted with the inner surface of capillary as chiral staionary phase. These two modes are called capillary zone electrophoresis and capillary electrochromatography, respectively. The use of cyclodextrins (CDs) for different host-guest complex of enantiomeric pairs of compounds is by far the most common strategy employed for chiral separation by capillary electrophoresis.
To solve the problems said above, in this paper, a simpler reaction steps, a cheaper, and a more soluble derivatives ofβ-cyclodextrin (β-CD) was synthesized. This compound also had Si-O bond, which can be reacted with the innfer surface of capillary easily. The substituted degree of this novel chiral selector, sulfated copolymer of acrylamide-β-Cyclodextrin (SPA-β-CD) is homogenous in statistics. In other words, although the substituted degree of every CD in a polymer chain is different, there are no obvious differences of the degree among polymer chains. The product was added into buffer as chiral additive and reacted with the inner surface of capillary respectively. These two modes have very different effect on EOF. For chiral separation, several chiral drugs were separated under different pH value in these two modes. The result shows, both modes have achieved chiral separation, but separation efficiencies of different drugs in the same mode are different. Also, the efficiencies of the same drugs with different mode are different.
Furthermore, with the combination of sigle-step electrospray method and sol-gel reaction, nanoparticles bonded with SPA-β-CD were prepared. It was added in buffer. And the result shows, it depressed the EOF of the system. Besides, warfarin was separated with tailing area. So, the ability of these nanoparticles in chiral separation is still to be improved. Thus, it is important to improve the reaction degree of silicane coupling agent and SPA-β-CD
为了解决定位反应的磺酸化环糊精以上不足,本文在大量研究的基础上,设计了含有硅氧键的磺酸化β—环糊精这一分子结构,从统计学和高分子的角度,获得了在电泳中均一化的环糊精。并可以通过硅氧键与毛细管壁键合。所得到产品同样可以获得较好的水溶性。通过对比产品作为手性添加剂和手性固定相在不同pH条件下对电渗流的抑制作用,考察了其电泳行为。在电色谱形式下对电渗流的抑制作用非常明显；作为添加剂时在整个考察pH区间内,电渗流变化平缓。在不同pH值条件下考察pH环境分别对几种代表性手性药物的分离作用,结果显示有的获得了手性分离效果,有的两种对映体在出峰时间上有明显区别。对比其不同作用方式的作用结果,分别对不同药物具有手性分离能力,说明其在不同电泳模式下的作用能力、结合方式有很大差别。
利用实验室己建立的电喷雾制备纳米硅球技术,制备带有手性分离基团的纳米级微球。并将其作为手性添加剂考察对电渗流的抑制作用。对手性药物进行分离的过程中对所有的酸性药物无法分离。而对华法令的分离有拖尾现象,说明微球上确实键合上对手性药物具有分离能力的官能团,但其作用能力还非常有限。因此,在制球过程中如何提高硅烷偶联剂与产品的结合能力是制备中的关键技术。
In recent years, the separation of enantiomers is of primary importance in pharmaceutical analysis. The main advantage of electromigration techniques is the high efficiency due to the plug-like flow profile caused by the EOF. Furthermore, there is a low solvent and selector consumption. Chiral CE separations of drugs have two major modes:chiral selector is added in buffer as chiral additive, or chiral selector is reacted with the inner surface of capillary as chiral staionary phase. These two modes are called capillary zone electrophoresis and capillary electrochromatography, respectively. The use of cyclodextrins (CDs) for different host-guest complex of enantiomeric pairs of compounds is by far the most common strategy employed for chiral separation by capillary electrophoresis.
To solve the problems said above, in this paper, a simpler reaction steps, a cheaper, and a more soluble derivatives ofβ-cyclodextrin (β-CD) was synthesized. This compound also had Si-O bond, which can be reacted with the innfer surface of capillary easily. The substituted degree of this novel chiral selector, sulfated copolymer of acrylamide-β-Cyclodextrin (SPA-β-CD) is homogenous in statistics. In other words, although the substituted degree of every CD in a polymer chain is different, there are no obvious differences of the degree among polymer chains. The product was added into buffer as chiral additive and reacted with the inner surface of capillary respectively. These two modes have very different effect on EOF. For chiral separation, several chiral drugs were separated under different pH value in these two modes. The result shows, both modes have achieved chiral separation, but separation efficiencies of different drugs in the same mode are different. Also, the efficiencies of the same drugs with different mode are different.
Furthermore, with the combination of sigle-step electrospray method and sol-gel reaction, nanoparticles bonded with SPA-β-CD were prepared. It was added in buffer. And the result shows, it depressed the EOF of the system. Besides, warfarin was separated with tailing area. So, the ability of these nanoparticles in chiral separation is still to be improved. Thus, it is important to improve the reaction degree of silicane coupling agent and SPA-β-CD
引文
[1]陈义,毛细管电泳技术与应用第二版,北京：化学工业出版社,2006.1-2
[2]Altria K D. Overview of capillary electrophoresis and capillary electrochromatography. J. Chromatogr. A,1999,856:443～463
[3]Hadley M, Gilges M, Senior J, et al. Capillary electrophoresis in the pharmaceutical industry:applications in discovery and chemical development. J. Chromatogr. B,2000,745:177～188
[4]Petersen J R, Okorodudu A O, Mohammad A, et al. Capillary electrophoresis and its application in the clinical laboratory. Clinica Chimina Acta.,2003,330: 1-30
[5]Pico Y, Rodriguez R, Manes J. Capillary electrophoresis for the determination of pesticide residues. Trends in Analytical Chemistry,2003,22(3):133～151
[6]Dong Y. Capillary electrophoresis in food analysis. Trends in Food Science & Technology,1999,10:87～93
[7]Hjerten S. Free zone electrophoresis. Chromatogr Rev.,1967,9:122～219
[8]Everaerts F M. Zone elecrophoresis in capillary tubes. Sci Tools,1970, 17:25～36
[9]Virtanen R. Zone electrophoresis in a narrow-bore tube employing potentiometric detection. Acta Polytech Scand,1974,123:1-67
[10]Mikkers F E P. PEM concentration distribution in free zone electrophoresis. J. Chromatogr.,1979,169:1～10
[11]Jorgenson J W, Lukacs K D. Zone electrophoresis in opentubular glass capillaries. Anal Chem.,1981,53:1298～1302
[12]Hjerten S. High-performance electrophoresis:The electrophoretic counterpart of high-performance liquid chromatography. J Chromatogr.,1983, 270:1-6
[13]Hjerten S, Zhu M D. Adaptation of equipment for high-performance electrophoresis to isoelectric focusing. J Chromatogr.,1985,346:265～270
[14]Terabe S, et al. Electrokinetic separatins with micellar solutions and open-tubular capillaries. Anal Chem.,1984,56:111～113
[15]Lauer H H, Mcmanigill D. Capillary zone electrophoresis of proteins in untreated fused silica tubing. Anal Chem.,1986,58:166～175
[16]Pretorius V, Hopkins B J, Schieke J D. Electro-osmosis:A new concept for high-speed liquid chromatography. J. Chromatogr.,1974,99:23-30
[17]Jorgensen J W, Lukacs K D. High-resolution separations based on electrophoresis and electroosmosis. J. Chromatogr.,1981,218:209-216
[18]Tsuda T, Nomura K, Nakagawa G. Open-tubular microcapillary liquid chromatography. J. Chromatogr.,1982,248:241～247
[19]沈淑君,毛细管电色谱技术及应用的最新进展,2008,10(1)：17～20
[20]袁瑞娟,王怀锋,刘丹宁等,毛细管电色谱技术研究进展,化学进展,2006,18(9)：1181～1186
[21]DENG Y. L, et al. Theoretical and experimental consideration of chromatographic behavior in pressurized flow driven electrochromatography. Chin J Anal Chem,1998,26(12):271～275
[22]林炳承,毛细管电泳导论,北京：科学出版社,1996.5～6
[23]Jorgenson J W, Lukas K D. Zone electrophoresis in open-tubular glass-capillaries. Anal. Chem.,1981,53(8):1298～1302
[24]Rice L, Whitehead R. Electrokinetic flow in a narrow cylindrical capillary. J. Phys.Chem.,1965,69:4017～4024
[25]Knox J H, Grant I H. Miniaturisation in pressure and electroendosmotically driven liquid chromatography:some theoretical consideration. Chromatographia. 1987,24:135～143
[26]Adam T, Luedtke S, Unger K K. Packing and stationary phase design for capillary electroendosmotic chromatography (CEC). Chromatographia,1999,49: 49～55
[27]Luedtke S, Adam T, Doehren N, et al. Toward the ultimate minimum particle diameter of silica packings in capillary electrochromatography. J. Chromatogr. A, 2000,887:339～346
[28]Cikalo M Q Bartle K D, Myers P. Attempt to define the role of the length of the packed section in capillary electrochromatography. J. Chromatogr. A,1999,836: 25～34
[29]张丽华,邹汉法,施维等,中性溶质在反相毛细管电色谱中的保留行为,色谱,1998,16(2)：106～110
[30]Mueller T, Posch U C, Lindner H H. Separation of phenylthiohydantoin amino acids by capillary electrochromatography. Electrophoresis,2004,25: 578～585
[31]Crego L, Martinez J, Martina M L. Influence of mobile phase composition on electroosmotic flow velocity, solute retention and column efficiency in open-tubular reversed-phase capillary electrochromatography. J. Chromatogr. A, 2000,869:329～337
[32]Banholczer A, Pyell U. Some considerations concerning the composition of the mobile phase in capillary electrochromatography. J. Chromatogr. A,2000, 869,363-374
[33]Fu H J, Xie C H, Zou H F, et al. Monolithic columns with mixed modes of reversed-phase and anion-exchange stationary phase for capillary electrochromatography. J. Chromatogr. A,2004,1044:237～244
[34]Kenndler S E. Electrophoresis in fused-silica capillaries:the influence of organic solvents on the electroosmotic velocity and the zeta potential. Anal. Chem.,1991,63:1801～1804
[35]Hatajik T D, Brown P R. Chiral separations of pharmaceticals using capillary electrochromatography (CEC):An overview. J. Cap. Electrophoresis.1998, 5:143～151
[36]Fanali S. Identification of chiral drug isomers by capillary electrophoresis. J. Chromatogr. A,1996,735:77～121
[37]Caldwell J. Chrial pharmacology and the regulation of new drugs. J. Chem. & Indu.,1995, (5):176～179
[38]Schweitz L, Andersson L I, Nilsson S. Capillary electrochromatography with predetermined selectivity obtained through molecular imprinting. Anal. Chem.1997,69(6):1179～1183
[39]邹汉法,刘震,叶明亮等,毛细管电色谱及其应用,北京：科学出版社,2001,207～208
[40]Nishi H. Enantioselectivity in chiral capillary electrophoresis with polysaccharides. J. Chromatogr. A,1997,792:327～347
[41]Bjornsdottir I, Hansen S H, Terabe S. Chiral separation in non-aqueous media by capillary electrophoresis using the ion-pair principle. J. Chromatogr. A, 1994,745:37-44
[42]Armstrong D W, Tang Y, Chen S. Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography. Anal. Chem.,1994,66:1473～1484
[43]Gotti R, Cavrini V, Andrisano V, et al, Dermatan sulfate as useful chrial selector in capillary electrophoresis. J. Chromatogr. A,1998,814:205～211
[44]Agyei N M, Gahm K H, Stalcup A M. Chiral separations using heparin and dextran sulfate in capillary zone electrophoresis. Anal. Chem. Acta,1995,307: 185～191
[45]Gotti R, Cavrini V, Andrisano V, et al. Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis. J. Chromatogr. A,1999,845: 247～256
[46]Kuhn R, Erni F, Bereuter T. Chiral recognition and enantiomeric, resolution based on host-guest complexation with crown-ethers in capillary zone Electrophoresis. Anal. Chem.,1992,64:2815～2820
[47]Mori Y, Ueno K, Umeda T. Enantiomer separation by capillary electrophoresis using DEAE-dextran and aminoglycosidin antibiotics. J. Chromatogr. A,1997,757:328～332
[48]Gassmann E, Kuo J E, Zare R N. Electrokinetic resolution of amino acid enatiomers with copper(II)-aspartame support electrolyte. Science,1985,230: 813～814
[49]童林荟,环糊精化学——基础与应用,北京：科学出版社,2001,17～18
[50]Jannini G M, Isaaq H J. Micellar electrokinetic capillary chromatogramphy: basic considerations and current trends. J. Liq. Chromatogr.,1992,15:927～960
[51]Rizzi A, Schuh R, Bruckner A, et al. Enantiomeric resolution of galanthamine and related drugs used in Alzheimer therapy by capillary zone electrophoresis employing derivatized cyclodextrin selectors. J. Chromatogr. B, 1999,730:167～175
[52]Pak C, Marriott P J, Carpenter P D. Enantiomeric separation of propranolol and selected metabolltes by using capillary electrophoresis with hydroxypropyl-β-cyclodextrin as chiral selector. J. Chromatogr.1998,793:357-364
[53]Koppenhoefer B, Epperlein U, Schlunk R, et al. Separation of enantiomers of drugs by capillary electro-phoresis. V. Hydroxy-propyl- -cyclodextrin as chiral solvating agent. J. Chromatogr. A,1998,793(1):153～164
[54]Miura M, Terashita Y, Funazo K, et al. Separation of phenoxy acid herbicides and their enantiomers in the presence of selectively methylated cyclodextrins by capillary zone electrophoresis. J. Chromatogr. A,1999,846: 359～367
[55]Lurie I S, Klein R F K, Dal Cason T A, et al. Chiral resolution of cationic drugs of forensic interest by capillary electrophoresis, with mixtures of neutral and anionic cyclodextrins. Anal.Chem.,1994,66:4019～4026
[56]Tait R J, Thompson D O, Stella V J, et al. Sulfobutyl Ether-β-Cyclodextrin as a chiral discriminator for use with capillary electrophoresis. Anal.Chem., 1994,66:4013～4018
[57]Morin P, Bellessort D, Dreux M et al. Chiral resolution of funcyionalized piperidine enantiomers by capillary elector-phoresis with native, alkylated and anionic β-cyclodextrins. J. Chromatogr. A,1998,796(2):375-383
[58]陆豪杰,阮宗琴,欧庆瑜,手性添加剂磺丁基—β—环糊精的合成及毛细管电泳手性分离,分析测试学报,,2000,19(5)：16～19
[59]Schurig V, Jung M, Mayer S, et al. Unified enantioselective capillary chromatography on a Chirasil-DEX stationary phases. Advantages of column miniturization. J. Chromatogr.A,1995,694:119～128
[60]Jakubetz H, Czesla H, Schurig V. On the feasibility of miniaturized enantiomeric separation by liquid chromatography (OTLC) and open tubular electrochromatography (OTEC). J. Microcolumn Sep.,1997,9:421～431
[61]Leliever F, Yan C, Zare R N, et al. Capillary electrochromatography: operating characteristics and enantiomeric separations. J. Chromatogr. A,1996, 723:145～156
[62]Deng Y, Zhang J, Tsuda T, et al. Modeling and optimization of enantioseparation by capillary electrochromatography. Anal. Chem.1998, 70:4586～4593
[63]朱军,邹汉法,施维等,中国科学(B辑)。1999,29：418～425
[64]Vincent J B, Sokolowski A D, NguyenT. A family of single-isomer chiral resolving agents for capillary electrophoresis: 1. Heptakis (2,3-di-6-sulfato)-beta.-cyclodextrin. Anal. Chem.,1997,69:4226～4233
[65]Vincent, J B, Kirby D M, Nguyen T V, et al. A family of single-isomer chiral resolving agents for capillary electrophoresis:2. hepta-6-.sulfato-b-cyclodextrin. Anal. Chem.,1997,69 (21):4419～4428
[66]Cai H, Nguyen T V, Vigh Gy, A family of single-isomer chiral resolvingagents for capillary electrophoresis:3. Heptakis (2, 3-dimethyl-6-sulfato)-.beta.-cyclodextrin. Anal. Chem.,1998,70:580～589
[67]O'Keeffe F, Shamsi S A, Darcy R, et al. A persubstituted cationic beta-cyclodextrin for chiral separations. Anal.Chem.,1997,69:4773～4782
[68]Chen F T, Shen Q Evangelista R A. Characterization of highly sulfated cyclodextrins. J. Chromatogr. A,2001,924:523～532
[69]Chen F T. Interactions of Enantiomers of aromatic amino acids with highly sulfated cyclodextrins. LCGC North America,2003,21:366～374
[70]Chen F T, Evangelista R. Highly sulfated cyclodextrins:The solution for chiral analysis. American laboratory,2002,8:30～37
[71]Stalcup A M, Gahm K H. Applications of sulfated cyclodextrins to chiral separations by capillary zone electropboresis. Anal. Chem.,1996,68:1360～1368
[72]Fu-Tai A. Chen, Gene Shen, Ramon A. Evangelista, Characterization of highly sulfated cyclodextrins. J. Chromatogr. A,2001(942):523～532
[73]Takashi Koide, Kyoji Ueno. Enantiomeric separations of cationic and neutral compounds by capillary electrochromatography with monolithic chiral stationary phases of β-cyclodextrin-bonded negatively charged polyacrylamide gels. J. Chromatogr. A,2000 (893):177-187
[74]Dorothee Wistuba, Volker Schurig. Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography. J. Chromatogr. A,2000 (875): 255-276
[75]E.S.威尔克斯,工业聚合物手册,北京：化学工业出版社,2006,512～513
[76]张邦华,朱常英,郭天瑛,近代高分子科学,北京：化学工业出版社,2006,214
[77]Towns J K, Bao J, Regnier F E. Synthesis and evaluation of epoxy polymer coating for the analysis of proteins by capillary zone electrophoresis. J. Chromatogr., 1992,599:227～237
[78]St. Pierre, L.A, Sentell, K.B. Cyclodextrins as enantioselective mobile. Phase modifiers for chiral capillary electrophoresis. Effect of pH and cyclodextrin concentration. J. Chromatogr.,1994,657:291-300
[79]王妍,新型手性选择剂的合成及其在电泳中的应用研究：[硕士学位论文],天津,天津大学药物科学与技术学院,2007
[80]Chow G M, Gonsalves K E. Nanoscience and nanotechnology, a perspective with chemistry examples. In Nanotechnology, ACS Symposium Series,662; ACS Books Department:Washington D.C., USA,1996:1-2
[81]Roco M C. Reviews of national research programs in nanoparticle and nanotechnology research in the U.S.A. J. Aerosol Science,1998,29:749～751
[82]黄飞,黄英,纳米粉体材料的研究及应用,材料导报,2005,5：114～118
[83]Suh J, Han B, Choi M. Highly charging of nanoparticles through electrospray of nanoparticles suspension. Journal of Colloid and Interface Science,2005,287: 135～140
[84]Smyth, W F. Recent studies on the electrospray ionisation mass spectrometric behaviour of selected nitrogen-containing drug molecules and its application to drug analysis using liquid chromatography-electrospray ionisation mass spectrometry. J. Chromatogr. B,2005,824:1-20
[85]Meng C K, Mann M, Fenn J B. Of protons or proteins. Zeitschrift fur Physik D Atoms, Molecules and Clusters,1988,10:361～368
[86]Loscertales I G. Device and procedure to generate steady compound jets of immiscible liquids and micro/nanometric sized capsules. US2004069632,2004-04-15
[87]Taylor G I. Disintegration of water drops in an electric field. Proceedings of the Royal Society A,1964,280:383-397
[88]Alfonso M, Ganan C, Antonio B. The supercritical nature of electrohydrodynamically driven:capillary microjets emittedin the EHD spraying of liquid. J. Aerosol Sci.,1996,27, Suppl. I:215～216
[89]Chen D R, Pui D Y H, Kaufman S L. Electrospraying of conducting liquids for monodisperse aerosol generation in the 4nm to 1.8μm diameter range. J. Aerosol Sci., 1995,26(6):963～977
[90]Borra J P, Camelot D, Marijnissen J C M, et al, New aerosol generator based on the mixing of droplets through electrical forces:Production of particles with controlled properties. J. Aerosol Sci.,1996,27, Suppl. I:181～182
[91]杨新立,王俊德,熊博晖,高效液相色谱用硅质填料的进展,色谱,2000,18(4)：308～312
[92]吴晶,电喷雾法一步制备含键合相纳米微球的研究：[硕士学位论文],天津,天津大学药物科学与技术学院,2006
[93]Ding G S, Da Z L, Bao J J, et al, Reversed-phase and weak anion-exchange mixed-mode silica-based monolithic column for capillary electrochromatography, Electrophoresis,2006,27:3363～3372
[2]Altria K D. Overview of capillary electrophoresis and capillary electrochromatography. J. Chromatogr. A,1999,856:443～463
[3]Hadley M, Gilges M, Senior J, et al. Capillary electrophoresis in the pharmaceutical industry:applications in discovery and chemical development. J. Chromatogr. B,2000,745:177～188
[4]Petersen J R, Okorodudu A O, Mohammad A, et al. Capillary electrophoresis and its application in the clinical laboratory. Clinica Chimina Acta.,2003,330: 1-30
[5]Pico Y, Rodriguez R, Manes J. Capillary electrophoresis for the determination of pesticide residues. Trends in Analytical Chemistry,2003,22(3):133～151
[6]Dong Y. Capillary electrophoresis in food analysis. Trends in Food Science & Technology,1999,10:87～93
[7]Hjerten S. Free zone electrophoresis. Chromatogr Rev.,1967,9:122～219
[8]Everaerts F M. Zone elecrophoresis in capillary tubes. Sci Tools,1970, 17:25～36
[9]Virtanen R. Zone electrophoresis in a narrow-bore tube employing potentiometric detection. Acta Polytech Scand,1974,123:1-67
[10]Mikkers F E P. PEM concentration distribution in free zone electrophoresis. J. Chromatogr.,1979,169:1～10
[11]Jorgenson J W, Lukacs K D. Zone electrophoresis in opentubular glass capillaries. Anal Chem.,1981,53:1298～1302
[12]Hjerten S. High-performance electrophoresis:The electrophoretic counterpart of high-performance liquid chromatography. J Chromatogr.,1983, 270:1-6
[13]Hjerten S, Zhu M D. Adaptation of equipment for high-performance electrophoresis to isoelectric focusing. J Chromatogr.,1985,346:265～270
[14]Terabe S, et al. Electrokinetic separatins with micellar solutions and open-tubular capillaries. Anal Chem.,1984,56:111～113
[15]Lauer H H, Mcmanigill D. Capillary zone electrophoresis of proteins in untreated fused silica tubing. Anal Chem.,1986,58:166～175
[16]Pretorius V, Hopkins B J, Schieke J D. Electro-osmosis:A new concept for high-speed liquid chromatography. J. Chromatogr.,1974,99:23-30
[17]Jorgensen J W, Lukacs K D. High-resolution separations based on electrophoresis and electroosmosis. J. Chromatogr.,1981,218:209-216
[18]Tsuda T, Nomura K, Nakagawa G. Open-tubular microcapillary liquid chromatography. J. Chromatogr.,1982,248:241～247
[19]沈淑君,毛细管电色谱技术及应用的最新进展,2008,10(1)：17～20
[20]袁瑞娟,王怀锋,刘丹宁等,毛细管电色谱技术研究进展,化学进展,2006,18(9)：1181～1186
[21]DENG Y. L, et al. Theoretical and experimental consideration of chromatographic behavior in pressurized flow driven electrochromatography. Chin J Anal Chem,1998,26(12):271～275
[22]林炳承,毛细管电泳导论,北京：科学出版社,1996.5～6
[23]Jorgenson J W, Lukas K D. Zone electrophoresis in open-tubular glass-capillaries. Anal. Chem.,1981,53(8):1298～1302
[24]Rice L, Whitehead R. Electrokinetic flow in a narrow cylindrical capillary. J. Phys.Chem.,1965,69:4017～4024
[25]Knox J H, Grant I H. Miniaturisation in pressure and electroendosmotically driven liquid chromatography:some theoretical consideration. Chromatographia. 1987,24:135～143
[26]Adam T, Luedtke S, Unger K K. Packing and stationary phase design for capillary electroendosmotic chromatography (CEC). Chromatographia,1999,49: 49～55
[27]Luedtke S, Adam T, Doehren N, et al. Toward the ultimate minimum particle diameter of silica packings in capillary electrochromatography. J. Chromatogr. A, 2000,887:339～346
[28]Cikalo M Q Bartle K D, Myers P. Attempt to define the role of the length of the packed section in capillary electrochromatography. J. Chromatogr. A,1999,836: 25～34
[29]张丽华,邹汉法,施维等,中性溶质在反相毛细管电色谱中的保留行为,色谱,1998,16(2)：106～110
[30]Mueller T, Posch U C, Lindner H H. Separation of phenylthiohydantoin amino acids by capillary electrochromatography. Electrophoresis,2004,25: 578～585
[31]Crego L, Martinez J, Martina M L. Influence of mobile phase composition on electroosmotic flow velocity, solute retention and column efficiency in open-tubular reversed-phase capillary electrochromatography. J. Chromatogr. A, 2000,869:329～337
[32]Banholczer A, Pyell U. Some considerations concerning the composition of the mobile phase in capillary electrochromatography. J. Chromatogr. A,2000, 869,363-374
[33]Fu H J, Xie C H, Zou H F, et al. Monolithic columns with mixed modes of reversed-phase and anion-exchange stationary phase for capillary electrochromatography. J. Chromatogr. A,2004,1044:237～244
[34]Kenndler S E. Electrophoresis in fused-silica capillaries:the influence of organic solvents on the electroosmotic velocity and the zeta potential. Anal. Chem.,1991,63:1801～1804
[35]Hatajik T D, Brown P R. Chiral separations of pharmaceticals using capillary electrochromatography (CEC):An overview. J. Cap. Electrophoresis.1998, 5:143～151
[36]Fanali S. Identification of chiral drug isomers by capillary electrophoresis. J. Chromatogr. A,1996,735:77～121
[37]Caldwell J. Chrial pharmacology and the regulation of new drugs. J. Chem. & Indu.,1995, (5):176～179
[38]Schweitz L, Andersson L I, Nilsson S. Capillary electrochromatography with predetermined selectivity obtained through molecular imprinting. Anal. Chem.1997,69(6):1179～1183
[39]邹汉法,刘震,叶明亮等,毛细管电色谱及其应用,北京：科学出版社,2001,207～208
[40]Nishi H. Enantioselectivity in chiral capillary electrophoresis with polysaccharides. J. Chromatogr. A,1997,792:327～347
[41]Bjornsdottir I, Hansen S H, Terabe S. Chiral separation in non-aqueous media by capillary electrophoresis using the ion-pair principle. J. Chromatogr. A, 1994,745:37-44
[42]Armstrong D W, Tang Y, Chen S. Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography. Anal. Chem.,1994,66:1473～1484
[43]Gotti R, Cavrini V, Andrisano V, et al, Dermatan sulfate as useful chrial selector in capillary electrophoresis. J. Chromatogr. A,1998,814:205～211
[44]Agyei N M, Gahm K H, Stalcup A M. Chiral separations using heparin and dextran sulfate in capillary zone electrophoresis. Anal. Chem. Acta,1995,307: 185～191
[45]Gotti R, Cavrini V, Andrisano V, et al. Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis. J. Chromatogr. A,1999,845: 247～256
[46]Kuhn R, Erni F, Bereuter T. Chiral recognition and enantiomeric, resolution based on host-guest complexation with crown-ethers in capillary zone Electrophoresis. Anal. Chem.,1992,64:2815～2820
[47]Mori Y, Ueno K, Umeda T. Enantiomer separation by capillary electrophoresis using DEAE-dextran and aminoglycosidin antibiotics. J. Chromatogr. A,1997,757:328～332
[48]Gassmann E, Kuo J E, Zare R N. Electrokinetic resolution of amino acid enatiomers with copper(II)-aspartame support electrolyte. Science,1985,230: 813～814
[49]童林荟,环糊精化学——基础与应用,北京：科学出版社,2001,17～18
[50]Jannini G M, Isaaq H J. Micellar electrokinetic capillary chromatogramphy: basic considerations and current trends. J. Liq. Chromatogr.,1992,15:927～960
[51]Rizzi A, Schuh R, Bruckner A, et al. Enantiomeric resolution of galanthamine and related drugs used in Alzheimer therapy by capillary zone electrophoresis employing derivatized cyclodextrin selectors. J. Chromatogr. B, 1999,730:167～175
[52]Pak C, Marriott P J, Carpenter P D. Enantiomeric separation of propranolol and selected metabolltes by using capillary electrophoresis with hydroxypropyl-β-cyclodextrin as chiral selector. J. Chromatogr.1998,793:357-364
[53]Koppenhoefer B, Epperlein U, Schlunk R, et al. Separation of enantiomers of drugs by capillary electro-phoresis. V. Hydroxy-propyl- -cyclodextrin as chiral solvating agent. J. Chromatogr. A,1998,793(1):153～164
[54]Miura M, Terashita Y, Funazo K, et al. Separation of phenoxy acid herbicides and their enantiomers in the presence of selectively methylated cyclodextrins by capillary zone electrophoresis. J. Chromatogr. A,1999,846: 359～367
[55]Lurie I S, Klein R F K, Dal Cason T A, et al. Chiral resolution of cationic drugs of forensic interest by capillary electrophoresis, with mixtures of neutral and anionic cyclodextrins. Anal.Chem.,1994,66:4019～4026
[56]Tait R J, Thompson D O, Stella V J, et al. Sulfobutyl Ether-β-Cyclodextrin as a chiral discriminator for use with capillary electrophoresis. Anal.Chem., 1994,66:4013～4018
[57]Morin P, Bellessort D, Dreux M et al. Chiral resolution of funcyionalized piperidine enantiomers by capillary elector-phoresis with native, alkylated and anionic β-cyclodextrins. J. Chromatogr. A,1998,796(2):375-383
[58]陆豪杰,阮宗琴,欧庆瑜,手性添加剂磺丁基—β—环糊精的合成及毛细管电泳手性分离,分析测试学报,,2000,19(5)：16～19
[59]Schurig V, Jung M, Mayer S, et al. Unified enantioselective capillary chromatography on a Chirasil-DEX stationary phases. Advantages of column miniturization. J. Chromatogr.A,1995,694:119～128
[60]Jakubetz H, Czesla H, Schurig V. On the feasibility of miniaturized enantiomeric separation by liquid chromatography (OTLC) and open tubular electrochromatography (OTEC). J. Microcolumn Sep.,1997,9:421～431
[61]Leliever F, Yan C, Zare R N, et al. Capillary electrochromatography: operating characteristics and enantiomeric separations. J. Chromatogr. A,1996, 723:145～156
[62]Deng Y, Zhang J, Tsuda T, et al. Modeling and optimization of enantioseparation by capillary electrochromatography. Anal. Chem.1998, 70:4586～4593
[63]朱军,邹汉法,施维等,中国科学(B辑)。1999,29：418～425
[64]Vincent J B, Sokolowski A D, NguyenT. A family of single-isomer chiral resolving agents for capillary electrophoresis: 1. Heptakis (2,3-di-6-sulfato)-beta.-cyclodextrin. Anal. Chem.,1997,69:4226～4233
[65]Vincent, J B, Kirby D M, Nguyen T V, et al. A family of single-isomer chiral resolving agents for capillary electrophoresis:2. hepta-6-.sulfato-b-cyclodextrin. Anal. Chem.,1997,69 (21):4419～4428
[66]Cai H, Nguyen T V, Vigh Gy, A family of single-isomer chiral resolvingagents for capillary electrophoresis:3. Heptakis (2, 3-dimethyl-6-sulfato)-.beta.-cyclodextrin. Anal. Chem.,1998,70:580～589
[67]O'Keeffe F, Shamsi S A, Darcy R, et al. A persubstituted cationic beta-cyclodextrin for chiral separations. Anal.Chem.,1997,69:4773～4782
[68]Chen F T, Shen Q Evangelista R A. Characterization of highly sulfated cyclodextrins. J. Chromatogr. A,2001,924:523～532
[69]Chen F T. Interactions of Enantiomers of aromatic amino acids with highly sulfated cyclodextrins. LCGC North America,2003,21:366～374
[70]Chen F T, Evangelista R. Highly sulfated cyclodextrins:The solution for chiral analysis. American laboratory,2002,8:30～37
[71]Stalcup A M, Gahm K H. Applications of sulfated cyclodextrins to chiral separations by capillary zone electropboresis. Anal. Chem.,1996,68:1360～1368
[72]Fu-Tai A. Chen, Gene Shen, Ramon A. Evangelista, Characterization of highly sulfated cyclodextrins. J. Chromatogr. A,2001(942):523～532
[73]Takashi Koide, Kyoji Ueno. Enantiomeric separations of cationic and neutral compounds by capillary electrochromatography with monolithic chiral stationary phases of β-cyclodextrin-bonded negatively charged polyacrylamide gels. J. Chromatogr. A,2000 (893):177-187
[74]Dorothee Wistuba, Volker Schurig. Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography. J. Chromatogr. A,2000 (875): 255-276
[75]E.S.威尔克斯,工业聚合物手册,北京：化学工业出版社,2006,512～513
[76]张邦华,朱常英,郭天瑛,近代高分子科学,北京：化学工业出版社,2006,214
[77]Towns J K, Bao J, Regnier F E. Synthesis and evaluation of epoxy polymer coating for the analysis of proteins by capillary zone electrophoresis. J. Chromatogr., 1992,599:227～237
[78]St. Pierre, L.A, Sentell, K.B. Cyclodextrins as enantioselective mobile. Phase modifiers for chiral capillary electrophoresis. Effect of pH and cyclodextrin concentration. J. Chromatogr.,1994,657:291-300
[79]王妍,新型手性选择剂的合成及其在电泳中的应用研究：[硕士学位论文],天津,天津大学药物科学与技术学院,2007
[80]Chow G M, Gonsalves K E. Nanoscience and nanotechnology, a perspective with chemistry examples. In Nanotechnology, ACS Symposium Series,662; ACS Books Department:Washington D.C., USA,1996:1-2
[81]Roco M C. Reviews of national research programs in nanoparticle and nanotechnology research in the U.S.A. J. Aerosol Science,1998,29:749～751
[82]黄飞,黄英,纳米粉体材料的研究及应用,材料导报,2005,5：114～118
[83]Suh J, Han B, Choi M. Highly charging of nanoparticles through electrospray of nanoparticles suspension. Journal of Colloid and Interface Science,2005,287: 135～140
[84]Smyth, W F. Recent studies on the electrospray ionisation mass spectrometric behaviour of selected nitrogen-containing drug molecules and its application to drug analysis using liquid chromatography-electrospray ionisation mass spectrometry. J. Chromatogr. B,2005,824:1-20
[85]Meng C K, Mann M, Fenn J B. Of protons or proteins. Zeitschrift fur Physik D Atoms, Molecules and Clusters,1988,10:361～368
[86]Loscertales I G. Device and procedure to generate steady compound jets of immiscible liquids and micro/nanometric sized capsules. US2004069632,2004-04-15
[87]Taylor G I. Disintegration of water drops in an electric field. Proceedings of the Royal Society A,1964,280:383-397
[88]Alfonso M, Ganan C, Antonio B. The supercritical nature of electrohydrodynamically driven:capillary microjets emittedin the EHD spraying of liquid. J. Aerosol Sci.,1996,27, Suppl. I:215～216
[89]Chen D R, Pui D Y H, Kaufman S L. Electrospraying of conducting liquids for monodisperse aerosol generation in the 4nm to 1.8μm diameter range. J. Aerosol Sci., 1995,26(6):963～977
[90]Borra J P, Camelot D, Marijnissen J C M, et al, New aerosol generator based on the mixing of droplets through electrical forces:Production of particles with controlled properties. J. Aerosol Sci.,1996,27, Suppl. I:181～182
[91]杨新立,王俊德,熊博晖,高效液相色谱用硅质填料的进展,色谱,2000,18(4)：308～312
[92]吴晶,电喷雾法一步制备含键合相纳米微球的研究：[硕士学位论文],天津,天津大学药物科学与技术学院,2006
[93]Ding G S, Da Z L, Bao J J, et al, Reversed-phase and weak anion-exchange mixed-mode silica-based monolithic column for capillary electrochromatography, Electrophoresis,2006,27:3363～3372