毛细管电泳拆分2-(9-蒽基)-2-羟基乙酸对映体

以羟丙基-β-环糊精为手性选择试剂,首次对外消旋的2-（9-蒽基）-2-羟基乙酸对映体的毛细管电泳分离进行了研究.比较了环糊精的种类、浓度、背景电解质的类型及pH对分离的影响.实验结果表明,采用15mmol/L羟丙基-β-环糊精为手性选择试剂,在20 mmol/L的三羟甲基氨基甲烷（Tris）-磷酸缓冲体系中（pH6.0）,2-（9-蒽基）-2-羟基乙酸对映体达到基线分离,分离度为1.58.     

二甲基-β-环糊精作为手性选择剂对尼索地平对映体的毛细管电泳拆分研究

以二甲基-β-环糊精(DM-β-CD)为手性添加剂,用毛细管电泳法对消旋体药物尼索地平进行拆分研究。考察了二甲基-β-环糊精浓度、背景电解质种类、缓冲溶液pH值、十二烷基硫酸钠(SDS)浓度、分离电压、温度对对映体分离的影响。结果表明,以pH 8.0的30 mmol/L磷酸二氢钠-磷酸氢二钠溶液(含38mmol/L二甲基-β-环糊精,30 mmol/L SDS)为缓冲液,分离电压15 kV,毛细管温度18℃,检测波长254 nm时,尼索地平对映体达到最佳分离,分离度为1.95,对映体迁移时间分别为13.0、13.54 min。该方法简单、快速、经济,可用于尼索地平对映体的手性分离。     

β-环糊精用于毛细管电泳拆分佐匹克隆对映体的研究

以β-环糊精(β-CD)为手性添加剂,用毛细管区带电泳法对手性药物佐匹克隆进行了拆分研究.考察了β-环糊精浓度、背景电解质组成、浓度及pH值、分离电压、温度等对对映体分离的影响.结果表明,以pH 2.5的100 mmol/L三羟甲基氨基甲烷-磷酸溶液(含15 mmol/L β-环糊精)为运行缓冲液,分离电压28 kV,毛细管温度16 ℃,检测波长303 nm,佐匹克隆对映体达到最佳分离,分离度为2.7,对映体迁移时间分别为8.4、8.9 min.该方法简单、快速、经济,可适用于佐匹克隆对映体的手性分离.     

2-(9-蒽基)-2-羟基乙酸的毛细管电泳分离研究

以β-环糊精及其衍生物为手性选择试剂,采用高效毛细管电泳法对外消旋的2-(9-蒽基)-2-羟基乙酸进行了手性分离。研究了手性选择剂的种类、浓度,背景电解质的pH值等因素对对映体分离的影响。实验结果表明,采用55 g/L的磺化-β-环糊精为手性选择试剂,在pH 2.5的10 mmol/L三羟甲基氨基甲烷(Tris)-磷酸缓冲体系中,2-(9-蒽基)-2-羟基乙酸对映体可得到良好的分离。     

加压毛细管电色谱法分离1-甲基-3-苯基丙胺对映体

运用毛细管电色谱(pCEC)模式,以羟丙基-β-环糊精(HP-β-CD)作为手性选择剂,对1-甲基-3-苯基丙胺对映体进行手性分离。1-甲基-3-苯基丙胺对映体在最佳的条件下如:手性选择剂浓度10g/L、流动相配比:V(乙腈)∶V(磷酸盐体系)=60∶40溶液(5mmol/L)、背景电解质pH=7.6、柱温16℃和分离电压10kV达到了基线分离,该方法重现性好、简便、快捷。     

3-苯基乳酸的手性毛细管电泳拆分

考察了环糊精种类、环糊精浓度、缓冲溶液pH、分离电压、温度等因素对3-苯基乳酸手性分离的影响,并对分离条件进行了优化。结果表明,采用区带毛细管电泳技术,以0.03 mol/L的羟丙基-β-环糊精为手性选择剂,0.1 mol/L的磷酸缓冲溶液(pH 5.5)为电泳缓冲溶液,26 kV的分离电压,在25 ℃下可使3-苯基乳酸对映体达到基线分离,分离度为1.51。     

毛细管电泳法和高效液相色谱法拆分联萘二酚酸对映体

采用毛细管电泳法和高效液相色谱法直接拆分2,2′-二羟基-1,1′-联二萘-3,3′-二甲酸(HBNC)对映体.以四种不同的β-环糊精为手性添加剂,考察环糊精的种类与浓度、缓冲液pH值及浓度、分离电压、温度等因素对HBNC分离的影响.结果表明:采用10 mmol/L磺丁基醚-β-环糊精+20 mmol/L磷酸盐缓冲液(pH=7.0),20 kV分离电压,HBNC对映体在20 min内达到基线分离,分离度达到3.31.采用(S)-叔-亮氨酸基-(S)-1-(α-萘基)乙胺手性柱,正己烷-乙醇-三氟乙酸(97∶3∶0.2,V/V)流动相,HBNC对映体在40 min内也基本达到基线分离.     

聚合-β-环糊精作手性选择剂的毛细管电泳法分离4种光学活性农药中间体

以聚合-β-环糊精作为毛细管区带电泳手性选择剂,成功分离了2-苯氧丙酸(PPA)、顺式-功夫菊酸(cis-PA)、1-苯基-2-(对甲苯基)乙胺(PTE)和1-苯基-2-(对甲氧基苯基)乙胺(PME)4种光学活性农药中间体的对映体。考察了不同手性选择剂及其浓度、背景电解质的pH等操作条件对分离的影响。结果表明,在12kV操作电压下、30mmol／Ltris-HCl背景电解质中,用14g／L聚合-β-CD作为手性选择剂,PPA和cis-PA对映体在pH6．0时,PIE和PME对映体分别在pH2．5和pH3．0时可以被较好分离。在优化的分离条件下,用聚合-β-CD作毛细管区带电泳手性选择剂分离PIE对映体的分离度为1．513,成功测定了两种旋光性PIE的对映体过量值。     

扁桃酸甲酯对映体的毛细管电泳手性拆分

采用β-环糊精及其衍生物作为手性选择剂，对扁桃酸甲酯对映体进行毛细管电泳分离，考察了不同环糊精种类和浓度、背景电解质类型及pH对分离效果的影响；实验结果表明，pH6．0、50g／L磺酸化环糊精(Su-β-CD)、20mmol/L Tris的磷酸缓冲液，可以使扁桃酸甲酯对映体得到基线分离。     

氧氟沙星片剂和滴眼液中氧氟沙星对映体的毛细管电泳拆分及定量分析

采用环糊精及其衍生物为手性选择剂在CE上对氧氟沙星对映体进行了分离，研究了环糊精种类、浓度、分离电压、温度对分离的影响．重点考察了氧氟沙星的定量线性范围、检测限和重现性，在20-200mg／L浓度范围内，迁移时间重现性的相对标准偏差(RSD)控制在1．13％以内，峰面积重现性的RSD控制在4．3％以内，检测限为1mg／L．结果表明用20mmo1／L二甲基-β-环糊精(DM-β-CD)为手性选择剂，背景电解质为50mmo1／L Na2HPO4，pH＝3．0，不加有机添加剂情况下可得到较好的分离效果．同时，对氧氟沙星药品实样进行了分析，建主了一种市售氧氟沙星片剂和滴眼液中氧氟沙星对映体简单、快速的毛细管电泳分离、定量分析方法．     

固相萃取-毛细管电泳法测定兔血清中的山莨菪碱对映体

建立一种可用于定量的毛细管电泳法分离山莨菪碱对映体. 系统研究了三种手性选择剂: 羟丙基-β-环糊精 (HP-β-CD), 甲基-β-环糊精 (Me-β-CD), 羧甲基-β-环糊精(CM-β-CD) 及其浓度、缓冲溶液浓度和 pH 对山莨菪碱拆分的影响. 在110 mmol/L Tris-H3PO4缓冲液中加入20.0 mg/mL HP-β-CD和5.0 mg/mL CM-β-CD (pH 4.0)条件下, 山莨菪碱的4个对映体达到基线分离. 血清样品通过固相萃取预处理和浓缩, 对映体的固相萃取回收率在82.9%～90.7%, 相对标准偏差RSD%均小于7 %. 山莨菪碱的4个对映体血标准溶液浓度与电泳峰面积在77.86～0.39 μg/mL范围内呈良好的线性, r≥0.999, 检出限(S/N＝3)为0.08 μg/mL. 平均日间和日内精密度(RSD% )分别小于6.1% 和4.8%, 方法回收率为97.4% 和105.4%. 建立的方法准确、可靠, 应用于监测兔连续3 d口服75 mg 山莨菪碱后血清中山莨菪碱的血药浓度, 结果满意.     

Method development and validation for the separation and determination of omeprazole enantiomers in pharmaceutical preparations by capillary electrophoresis

A new capillary zone electrophoresis (CZE) method for the separation of omeprazole enantiomers has been developed. Methyl-β-cyclodextrin (methyl-β-CD) was chosen as the chiral selector, and several parameters, such as cyclodextrin structure and concentration, buffer concentration, pH, and capillary temperature were investigated in order to optimize separation and run times. Analysis times, shorter than 8 min were found using a background electrolyte solution consisting of 40 mM phosphate buffer adjusted to pH 2.2, 30 mM β-cyclodextrin and 5 mM sodium disulphide, hydrodynamic injection, and 15 kV separation voltage. Detection limits were evaluated on the basis of baseline noise and were established 0.31 mg/l for the omeprazole enantiomers. The proposed method was applied to five pharmaceutical preparations with recoveries between 84 and 104% of the labeled contents.     

Determination of fenfluramine enantiomers in pharmaceutical formulations by capillary zone electrophoresis

Summary Capillary zone electrophoresis has been used for the enantiomeric separation of racemic ortho-fenfluramine and meta-fenfluramine employing a phosphate buffer at pH 2.5 added with cyclodextrins. The cyclodextrin type and concentration strongly influenced the chiral resolution. The uncharged β-cyclodextrin polymer gave enantiomeric resolution of both ortho and meta isomers, while γ-cyclodextrin was a good chiral selector for only ortho-fenfluramine; heptakis-2,3,6-tri-O-methyl-β-cyclodextrin permitted base line separation of meta-fenfluramine enantiomers but only partial resolution of racemic ortho-fenfluramine. The optimized electrophoretic method was applied to the quantitative analysis of 1-meta-fenfluramine (minor component in the mixture) and d-meta-fenfluramine in a commercial pharmaceutical formulation. Good reproducibility for migration time and corrected peak areas (R.S.D. <0.8 % and <1.2 %, respectively) was achieved and the presence of the minor component of the mixture was found to be in accord to previous determinations performed by other analytical methods.     

Determination of fenfluramine enantiomers in pharmaceutical formulations by capillary zone electrophoresis

Summary Capillary zone electrophoresis has been used for the enantiomeric separation of racemic ortho-fenfluramine and meta-fenfluramine employing a phosphate buffer at pH 2.5 added with cyclodextrins. The cyclodextrin type and concentration strongly influenced the chiral resolution. The uncharged β-cyclodextrin polymer gave enantiomeric resolution of both ortho and meta isomers, while γ-cyclodextrin was a good chiral selector for only ortho-fenfluramine; heptakis-2,3,6-tri-O-methyl-β-cyclodextrin permitted base line separation of meta-fenfluramine enantiomers but only partial resolution of racemic ortho-fenfluramine. The optimized electrophoretic method was applied to the quantitative analysis of 1-meta-fenfluramine (minor component in the mixture) and d-meta-fenfluramine in a commercial pharmaceutical formulation. Good reproducibility for migration time and corrected peak areas (R.S.D. <0.8% and <1.2%, respectively) was achieved and the presence of the minor component of the mixture was found to be in accord to previous determinations performed by other analytical methods.     

毛细管电泳法手性拆分4种氨酸和2种手性药物对映体

以双(6-氧-β-羧甲基-1,4-丁烯二酸单酯)-β-环糊精(DOCB-β-CD）作为手性添加剂,利用毛细管电泳对氨基酸和手性药物对映体进行拆分研究。 以20 mmol/L磷酸盐为缓冲溶液,考察了手性添加剂的浓度及缓冲溶液的pH值与分离电压等对拆分效果的影响,并在其优化条件下,实现了4种DL-氨基酸（苯丙氨酸、色氨酸、酪氨酸和组氨酸）以及手性药物（罗格列酮和酮洛芬）对映体的基线分离。     

Optimization of a capillary electrophoresis method to determine the chiral purity of a drug

Capillary electrophoresis (CE) using hydroxypropyl-β-cyclodextrin (HP-β-CD) in the separation buffer was investigated to determine the overall chiral purity of a drug containing a single stereogenic center. The effects of primary factors —pH, buffer components, buffer concentration, cyclodextrin concentration and sample amount (concentration and injection volume) — on the resolution of the enantiomers were investigated. Secondary factors such as the HP-β -CD source, lot and degree of substitution that were expected to affect the robustness of the assay were investigated also. The linearity, quantitation limit for the trace enantiomer and the precision of the measurements were determined. This study shows that understanding and optimizing the assay conditions leads to a chiral CE separation that is comparable to that obtained by chiral HPLC. However, chiral CE separations achieved with buffer additives have the advantages of shorter run times, higher numbers of theoretical plates (greater resolution), smaller amounts of chiral additive (less cost) and greater ruggedness (separation virtually independent of column properties unlike HPLC).     

α-萘基缩水甘油醚对映体的毛细管区带电泳手性拆分

建立了毛细管区带电泳手性拆分α-萘基缩水甘油醚对映体的方法.考察了不同手性拆分试剂对手性选择性的影响,实验结果表明,20 mmol/L H3PO4-三乙醇胺(pH 2.5)、2%(w/V)HS-β-CD、毛细管温度20 ℃、运行电压-18 kV为最佳分离条件,在该分离条件下α-萘基缩水甘油醚对映体实现基线分离.方法简便、准确,可用于α-萘基缩水甘油醚的手性拆分和对映体过量值(ee,%)测定.     

Chiral separation of basic drugs by capillary electrophoresis with carboxymethylcyclodextrins

Capillary electrophoresis (CE) with carboxymethylated beta- or gamma-cyclodextrins was used to achieve the rapid enantiomeric separation of a set of basic drugs. The enantiomers of 12 chiral amino-containing pharmaceutical compounds belonging to various therapeutic categories were analyzed by CE using an uncoated 60 cm x 75 microm I.D. silica capillary. Several experimental parameters such as the nature, concentration and pH of the buffer, nature and concentration of the anionic cyclodextrin and temperature were studied in order to optimize the enantiomeric separation. The variation of the solute partition coefficient for the chiral selector, the enantioselectivity and resolution factors are used to assess the quality of the chiral separation. It is shown that the solute affinity for the chiral selector is not related to its enantioresolution factor. None of the two cyclodextrin selectors used was able to separate the whole set of basic drugs.     

新型三唑类抗真菌活性化合物毛细管电泳手性拆分及手性识别机理分子模拟研究

研究了7种新型三唑类抗真菌活性化合物的毛细管电泳法手性分离,利用计算机辅助分子模拟技术研究拆分机理。考察了8种中性环糊精手性添加剂,只有2,6-二甲基-β-环糊精对7种活性化合物都有手性识别能力。在30mmol/L NaH2PO4缓冲液中含2,6-二甲基-β-环糊精30mmol/L,用H3PO4调至pH 2.2,温度20℃,电压20kV,在此条件下7种活性化合物都能达到手性分离,其中4种活性化合物能达到基线分离(Rs>1.5)。应用计算机辅助分子模拟软件Discovery Studio 2.5/Sybyl/Gold模拟2,6-二甲基-β-环糊精与7种活性化合物主客体包结过程,并计算相互结合能,探讨手性识别机理,发现拆分结果与结合能的差异有关,结合能差异越大拆分结果越好。