肖溶,杜培刚,罗月影,赵欣
XIAO Rong,DU Peigang,LUO Yueying,ZHAO Xin(Clinic Pharmacy Laboratory

• 1:水钢总医院临床药学实验室

摘要(Abstract)：

目的:研究羧甲基-β-环糊精取代度对毛细管电泳手性拆分普罗帕酮和普萘洛尔对映体的影响。方法:在氢氧化钠溶液中β-环糊精被氯乙酸直接羧甲基化,很方便地合成了不同取代度的羧甲基-β-环糊,并应用红外光谱和核磁共振对它们的平均取代度和取代位置进行表征,以不同取代度的羧甲基-β-环糊精为手性选择剂,系统考察运行缓冲液的浓度和pH值、手性选择剂浓度、石英毛细管温度和运行电压等因素对毛细管电泳手性拆分的影响。结果:随着羧甲基-β-环糊精取代度的增大,普罗帕酮和普萘洛尔对映体的分离随之改善;在优化条件下,两个消旋化合物都获得很好的拆分。结论:羧甲基-β-环糊精的取代度对毛细管电泳手性拆分和运行缓冲液的离子强度有重要影响,因此在手性分离中使用表征清晰的环糊精衍生物是非常重要的。
Objective:To study the effect of substitution degree(SD) of carboxymethyl-β-cyclodextrin(CM-β-CD) on chiral separations of propafenone enantiomers with capillary electrophoresis(CE).Methods: Carboxymethylation of cyclodextrin was made by monochloroacetic acid in sodium hydroxide solution,and several CM-β-CDs with various average SDs were synthesized.Average SDs and substitution positions of CM-β-CDs were characterized with infrared spectra(IR) and nuclear magnetic resonance(NMR).Effects of various parameters on enantioseparation including pH value,concentration of background electrolyte(BGE),capillary temperature,and applied voltage were investigated using CM-β-CDs with various average SDs and different substitution positions.Results: The enantioseparation of both propafenone and propranolol increased along with the increase of SD.High resolutions of two racemates were achieved under optimal conditions,respectively.Conclusions: SD has significant effect on the resolution of optical isomers and ionic strength of running buffer,hence the use of well characterized CD derivatives is crucial in enantioseparation.

关键词(KeyWords)： 普罗帕酮;普萘洛尔;手性拆分;羧甲基-β-环糊精;电泳,毛细管
propafenone;propranolol;enantioseparation;carboxymethyl-β-cyclodextrin;electrophoresis,capillary

Abstract:

Keywords:

基金项目(Foundation): 贵州省卫生厅科学技术基金项目(gzwkj2008-1-055);; 六盘水市科技攻关计划项目(52020-2008-1-05)

作者(Author): 肖溶,杜培刚,罗月影,赵欣
XIAO Rong,DU Peigang,LUO Yueying,ZHAO Xin(Clinic Pharmacy Laboratory

DOI: 10.19367/j.cnki.1000-2707.2010.02.011

参考文献(References)：

• [1]Juvancz Z,Kendrovics RB,Ivanyi R,et al.The role ofcyclodextrins in chiral capillary electrophoresis[J].Elec-trophoresis,2008(29):1701-1712.
• [2]Scriba GKE.Cyclodextrins in capillary electrophoresis en-antioseparations-Recent developments and applications[J].J Sep Sci,2008(31):1991-2011.
• [3]Wren SAC,Rowe RC.Theoretical aspects of chiral sepa-ration in capillary electrophoresisⅠ,Initial evaluation ofa model[J].J Chromatogr A,1992(603):235-241.
• [4]Szeman J,Ganzler K,Salgo A,et al.Effect of the substi-tution of cyclodextrin derivatives on chiral separations byhigh-performance liquid chromatography and capillary e-lectrophoresis[J].J Chromatogr A,1996(728):423-431.
• [5]傅小芸,孙翠荣,吕建德,等.羟丙基-β-环糊精的取代度和取代位置对毛细管电泳手性分离的影响[J].高等学校化学学报,1997(12):1957-1959.
• [6]卢铁刚,杨茂俊.羧甲基-β-环糊精手性流动相添加剂法拆分帕罗西汀及其中间体对映体[J].色谱,2007(11):830-833.
• [7]Kim HYUNMYUNG,Choi YOUNGJIN,Lim JUN,et al.Chiral separation of catechin by capillary electrophoresisusing mono-,di-,tri-succinyl-β-cyclodextrin as chiral se-lectors[J].Chirality,2009(21):937-942.
• [8]Kong DZ,Yang W,Duan KF,et al.Capillary electro-phoretic enantioseparation of m-nisoldipine using two dif-ferentβ-cyclodextrin[J].J Sep Sci,2009(32):3178-3183.
• [9]Reuben J,Rao CT,Pitha J.Distribution of substituentsin carboxymethyl ethers of cyclomaltoheptaose[J].Car-bohydr Res,1994(258):281-285.
• [10]Chen FTA,Shen G,Evangelista RA.Characterization ofhighly sulfated cyclodextrins[J].J Chromatogr A,2000(924):523-532.
• [11]Tongiani S,Velde DV,Ozeki T,et al.Sulfoalkyl ether-alkyl ether cyclodextrin derivatives,their synthesis,NMRcharacterization,and binding of 6α-methylprednisolone[J].J Pharm Sci,2005(94):2380-2390.
• [12]Stalcup AM,Gahm KH.Application of sulfated cyclo-dextrins to chiral separations by capillary zone electropho-resis[J].Anal Chem,1996(68):1360-1368.
• [13]Kwaterczak A,Duszczyk K,Bielejewska A.Comparisonof chiral separation of basic drugs in capillary electropho-resis and liquid chromatography using neutral and nega-tively charged cyclodextrins[J].Anal Chim Acta,2009(645):98-104.
• [14]Schmitt U,Ertan M,Holzgrabe U.Chiral capillary elec-trophoresis:facts and fiction on the reproducibility of res-olution with randomly substituted cyclodextrins[J].E-lectrophoresis,2004(25):2801-2807.

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