手性药物高效毛细管电泳拆分方法的研究进展

高效毛细管电泳法（high performance capillary electrophoresis,HPCE）在手性药物拆分领域得到了广泛的应用。目前,手性离子液体用于毛细管电泳拆分手性药物时,常与环糊精（CD）类手性选择剂构成二元体系产生协同作用,增强了手性离子液体潜在的手性拆分能力。依据对映体拆分的手性选择剂的种类及浓度、缓冲液的浓度和pH、电泳工作电压和温度,选出手性拆分的最佳条件。综述手性药物的发展以及应用HPCE拆分手性药物的文献资料,并对其研究的新进展作了分析。     

液液平衡手性萃取拆分的研究进展

目的 介绍液液平衡手性萃取拆分技术的基本原理,总结近年来液液平衡手性萃取拆分的研究进展。方法 根据手性选择剂的分类,对近年来液液平衡手性萃取拆分的最新应用研究情况做了介绍。结果 总结归纳了5大类手性选择剂的应用,包括过渡金属络合物、酒石酸衍生物、冠醚类、β-环糊精衍生物及金鸡纳碱类,并简要介绍了液液萃取拆分相关模型研究。结论 液液平衡手性萃取拆分技术分离效果良好,适用性强,易于实现工业规模,有望成为制备型分离外消旋体化合物的先进技术。     

手性选择剂及其在手性药物分离分析中的应用进展

色谱分离法是一种常用的手性拆分方法，它分为直接法和间接法。近年来，采用手性选择剂进行手性拆分的直接法发展迅速，应用广泛。本文则对几类常用的手性选择剂进行了综述，如环糊精、手性冠醚、大环糖肽类抗生素、线性多糖、蛋白质、手性表面活性剂及配体交换复合物等，阐述了其在药物手性分离分析领域中的应用和进展，并探讨了其手性识别机制。     

毛细管电泳手性拆分方法的研发策略

本文总结了毛细管电泳手性拆分的基本策略、分离条件选择策略、环糊精体系的选择,并提出毛细管电泳手性拆分方法的一般研究与开发策略,可为以后的毛细管电泳手性分离分析提供借鉴与思路。     

硫酸化环糊精在毛细管电泳手性拆分中的应用

综述近年来硫酸化环糊精在毛细管电泳手性药物拆分方面中的应用。对随机取代的硫酸化环糊精、单一异构体的硫酸化环糊精及多元环糊精体系的结构特点，及其在手性药物对映体拆分中的影响因素、条件优化和应用实例进行了讨论。硫酸化环糊精以良好的水溶性和强劲的手性识别能力应用于毛细管电泳的手性拆分，可使对映体获得较好的分离效果。     

以高取代磺酸基环糊精为手性选择剂毛细管电泳法拆分4种药物？…

目的：采用新型高取代磺酸基环糊精为毛细管电泳手性选择剂,研究萘普生、酮洛芬、氧氟沙星和阿托品４种药物的对映体分离。方法：在毛细管电泳仪上,以逆向区带电泳模式,研究３种高取代磺酸基环糊精手性选择剂对４种药物对映体拆分的影响,优化了分离条件,并探讨了分离机理。结果：在优化的条件下,４种物对映体取得很好的分离结果。结论：在毛细管电泳中,高取代磺酸基环糊精是一种很有潜力的手性选择剂,值得进一步研究。     

以高取代磺酸基环糊精为手性选择剂毛细管电泳法拆分4种药物对映体

目的 :采用新型高取代磺酸基环糊精为毛细管电泳手性选择剂 ,研究萘普生、酮洛芬、氧氟沙星和阿托品 4种药物的对映体分离。方法 :在毛细管电泳仪上 ,以逆向区带电泳模式 ,研究 3种高取代磺酸基环糊精手性选择剂对 4种药物对映体拆分的影响 ,优化了分离条件 ,并探讨了分离机理。结果 :在优化的条件下 ,4种药物对映体取得很好的分离结果。结论 :在毛细管电泳中 ,高取代磺酸基环糊精是一种很有潜力的手性选择剂 ,值得进一步研究。     

羧甲基-β-环糊精作为手性选择剂对毛细管电泳手性拆分西酞普兰的影响

目的 以羧甲基-β-环糊精作为手性选择剂,研究西酞普兰的毛细管电泳手性拆分方法 .方法 选择和优化了手性选择剂的浓度、缓冲溶液的浓度、pH及分离电压等.电泳石英毛细管柱内径为75 μm,总长65 cm,有效长度5 cm;紫外检测波长200 nm;柱温15℃.结果 在含0.25%羧甲基-β-环糊精和25 mmol·L<'-1>磷酸盐(pH7.0)的缓冲溶液中,分离电压为30kV时,西酞普兰对映体达到基线分离,分离度为1.6.结论 所建方法 可以分离分析西酞普兰对映体.     

高效毛细管电泳法研究合成山莨菪碱的手性分离

使用β－环胡及２，６－二羧甲基－β－环糊精为手性选择剂，采用高效毛细管电泳法对合成山莨菪碱的对映异构体的手性分离进行了研究。对影响手性分离的主要因素：手性选择剂，背景电解质，分离体系的酸度进行了系统的研究，为今后进一步研究合成山莨菪碱的手性分离奠定了基础。     

水溶性β-CD聚合物在毛细管电泳中分离手性药物罗格列酮和芬氟拉明

目的：建立了一种用毛细管电泳拆分罗格列酮和芬氟拉明两种药物对映体的方法。方法：以水溶性β-环糊精聚合物（β-CD polymer）为手性选择剂，采用毛细管区带电泳模式，考察了手性选择剂浓度、背景电解质溶液pH值、柱温及分离电压等因素对分离的影响。结果：在优化的实验条件下，两种药物的手性对映体均达到基线分离。结论：方法操作简单，重现性好，可用于这两种药物的质量控制。     

毛细管电泳手性拆分西他沙星异构体

目的:建立西他沙星及其异构体高效毛细管电泳拆分的新方法。方法:以β-环糊精及几种环糊精衍生物作为手性添加剂,采用毛细管电泳分离新型抗菌素西他沙星与其3个异构体。对运行缓冲液的浓度、pH,环糊精的种类、二元环糊精体系中环糊精的比例,分离电压,柱温,有机改性剂等因素对分离的影响进行考察,并对拆分机制进行初步探讨。结果:运行缓冲液为含2%硫酸化-β-环糊精和1%β-环糊精的25 mmol.L-1的磷酸二氢钾-磷酸缓冲溶液(pH 2.5),操作电压为-25kV,柱温为25℃,检测波长为295 nm,西他沙星与其3个异构体达到良好分离。结论:所建立的毛细管电泳方法简便,适用于西他沙星异构体的检查。     

A validated chiral CE method for Frovatriptan, using cyclodextrin as chiral selector

A cyclodextrin modified capillary zone electrophoretic method has been developed for the evaluation of chiral purity of Frovatriptan using sulfobutyl ether beta cyclodextrin (SB-beta-CD) as the chiral selector. The method is highly specific, accurate and reproducible. The method was optimized with a systematic method development approach by optimizing the pH of electrolyte, attempting the separation in different classes of chiral selectors and modifying parameters such as cyclodextrin concentration and the organic modifier type and concentration. The optimized method was validated for specificity, precision, linearity, accuracy and stability in solution using Imidazole as the internal standard. The limit of detection (LOD) and limit of quantification (LOQ) were 1.0 microg/mL and 5.0 microg/mL respectively for each isomer. The method was applied for estimating the chiral purity of various batches of Frovatriptan.     

Comparison of the miniaturised techniques capillary electrochromatography and capillary liquid chromatography for the chiral separation of chlorthalidone

The aim of this study was to compare the miniaturised techniques, capillary electrochromatography (CEC) and capillary liquid chromatography (CLC), for the chiral separation of chlorthalidone. In both cases, hydroxypropyl-beta-cyclodextrin was used as a chiral selector in the mobile phase, while an achiral stationary phase was used. Earlier, this separation was already optimised in CEC. Now, the separation was optimised in CLC. The influence of the organic modifier content and the cyclodextrin concentration on the separation was studied by means of a central composite design. Optimal separation conditions were determined, after response modelling, from the response surface contour plots. When these conditions were compared with those of the CEC optimisation, we can see the potential of using CLC as a chiral separation technique since less chiral selector was used, faster separations were obtained and better repeatability was observed in comparison with its electrical-driven counterpart.     

Enantioselective capillary electrophoretic separation of tryptophane- and tyrosine-methylesters in a dual system with a tetra-oxadiaza-crown-ether derivative and a cyclodextrin

Different dual selector systems containing a cyclodextrin derivative (methyl-beta-cyclodextrin and dimethyl-beta-cyclodextrin) and a new diaza-crown-ether derivative (N-[2-(1,4,10,13-tetraoxa-7,16-diazacyclooctadecan-7-yl)propanoyl]glycine) were studied in the enantioselective separation of tryptophan-methylester and tyrosine-methylester enantiomers. This paper deals with the systematic study of the effects of changing the composition of the background electrolyte on the resolution of the d- and l- forms using an experimental design approach. It was found that the dual systems allowed a better chiral separation of the amino acid derivatives. The experimental design approach also allowed improving the separation compared to the starting conditions (center point of the design), which were adopted from a previous study.     

Capillary electrochromatography for chiral separation and purity testing of pharmaceutical drug substances

Chiral separation of D,L-Norgestrel was successfully performed by cyclodextrin-modified capillary electrochromatographic (CEC) method. Optimized CEC conditions for purity testing were achieved: Hypersil C-18 packed capillary and 10 mM 2-[N-morpholino]-ethanesulfonic acid buffer (MES) and 40 v/v % methanol as background electrolyte containing 10 mM gamma-cyclodextrin at pH = 5.5. The resolution was found to be strongly dependent on the concentration of chiral selector gamma-cyclodextrin, applied voltage and temperature of the capillary. Our results represent a simple, fast and reproducible method for the separation of D,L-Norgestrel and purity testing of D-Norgestrel. It can be concluded that cyclodextrin modified HPLC, HPCE and CEC offer inexpensive, attractive and reliable chiral separation methods.     

环糊精及其衍生物在手性药物分离分析中的应用

有近一半的药物具有手性但通常两种异构体并不具有相同的药理活性,有一些异构体甚至具有毒性,因此,采用将手性药物良好分离的分析方法进行质控对药品的质量控制具有重要意义。环糊精及其衍生物是手性药物分离分析中常用的手性添加剂和手性固定相,本文对近年来环糊精及其衍生物在高效液相、气相、毛细管电泳、质谱、超临界流体等方面的应用进行综述。     

多聚乙酰神经氨糖酸毛细管电泳拆分新药马来酸氨氯地平对映体及手性分离机制

目的将多聚乙酰神经氨糖酸用作分离双氢吡啶类药物对映体的毛细管电泳手性选择剂，建立新药马来酸氨氯地平对映体的拆分方法。方法考察了手性选择剂浓度、运行缓冲液pH值、毛细管温度、工作电压和多糖分子量等因素对手性分离的影响。结果马来酸氨氯地平两对映体得到了完全分离，分离度为2.20，并研究了多聚乙酰神经氨糖酸对马来酸氨氯地平的手性识别机理。结论本法操作简便，可用于该新药对映体的分离分析。     

Modelling of conditions for the enantiomeric separation of beta2-adrenergic sympathicomimetics by capillary electrophoresis using cyclodextrins as chiral selectors in a polyethylene glycol gel

A two-factor central composite design was used to determine a mathematical model for prediction of the optimal conditions for the separation of the enantiomers of some widely used beta2-sympathicomimetic drugs (beta2-agonists) by capillary electrophoresis using cyclodextrins (CD) as a chiral selector in a polyethylene glycolgel. The effects of the chemical structure of these drugs along with the addition of polyethylene glycol to the cyclodextrin solution on the resolution of their enantiomers were studied. To allow impurity studies down to 0.1% (distomer eutomer) a resolution of 2.5 should be warranted. Those beta2-agonists containing two hydroxylic groups in the aromatic ring structure show the highest enantiomeric separation, due to the fact that one of their enantiomers has a better geometric structure to fit into the beta-cyclodextrin cavity.