用羧甲基聚合环糊精作手性剂的毛细管电泳法分离3种碱性药物

 采用 5种环糊精衍生物对碱性药物硫喷妥钠、盐酸氟桂利嗪、山梗菜碱进行了毛细管区带电泳的手性拆分。结果表明 ,采用含 2 % (质量分数 ,其余相同 )聚合 β 环糊精 (P β CD)或 0 5%羧甲基聚合 β 环糊精 (CM P β CD) 30mmol/L的Tris H3PO4缓冲液可使这 3种药物达到基线分离 ;使用CM P β CD时 ,分离度高达 4～35。     

手性药物的毛细管电泳拆分

以氧氟沙星、扑尔敏、特布它林和普萘洛尔为手性药物,分别采用羟丙基-β环糊精(HP--βCD)、羟丙基-β-环糊精结合羧甲基-β-环糊精(HP--βCD/CM--βCD)作手性拆分试剂,考察环糊精浓度和pH对手性选择性的影响。结果发现环糊精提供手性相互作用,而pH强烈地影响这种相互作用。以HP--βCD/CM-β-CD组成的双环糊精系统能更好地优化手性选择性,而通过调节pH可以获得需要的分离选择性、迁移次序。     

高效液相色谱手性流动相添加剂分离西孟坦对映体

以 β 环糊精作为手性流动相添加剂 ,研究了DL 西孟坦在反相HPLC系统中的拆分。考察了缓冲盐的浓度、pH、β 环糊精的浓度、流动相中甲醇的比例、流动相流速和温度对手性分离的影响 ,建立了 β 环糊精动态手性固定相法分离西孟坦对映体的方法。色谱条件为 :ZirchromKromasilODS 1(5 μm ,15 0mm× 4 .6mm)色谱柱 ,流动相为 2 0mmol/L磷酸盐缓冲液 (pH 6 .0 )含 12mmol/Lβ 环糊精∶甲醇 (70∶30 ,V/V) ,流速为 0 .8mL/min ,温度为 17℃。DL 西孟坦对映体的保留时间分别为 2 2 .5和 2 4 .5min ,分离度为 1.5 7。     

手性药物异丙嗪对映体的毛细管电泳-方波安培法检测

以未涂层融硅石英毛细管 (5 0cm× 75 μm)为分离柱 ,5mmol/LNaOH +10mmol/LCitricacid +3mmol/LH3 BO3 +10mmol/L β 环糊精 (β CD) (pH =3.5 )为电泳介质 ,分离电压 12kV ,采用毛细管电泳 方波安培法对手性药物异丙嗪对映体实现了分离检测。对影响手性对映体分离检测效果的缓冲溶液的种类、浓度和 pH等诸因素进行了研究。结果表明 :硼酸与手性选择剂 β CD分子中糖羟基发生键合配位作用 ,增加了β CD 的负电性的特性 ,在对映体拆分中起到关键性的作用。     

高效毛细管电泳拆分氯霉素前体

采用未涂层毛细管柱 (5 5cm× 5 0 μm) ,基于H3 BO3 与 β CD络合成大阴离子作为手性拆分试剂 ,在NaOH Cit溶液中加入 9 0mol/LH3 BO3 与 7 0mmol/L β CD(pH =3 0 )作为运行缓冲液 ,用高效毛细管电泳电导检测法对氯霉素前体 (PCP)进行了拆分研究。考察了影响分离的实验参数 ,同时对其拆分机理进行了初步探讨。结果表明 ,在选择的最佳实验条件下 ,氯霉素前体分子中 4个对映异构体在 2 0min内得到基线分离 ,所建立的方法分离条件简单 ,重现性好。     

芳基甘氨酰胺的手性毛细管电泳拆分

 研究了 9种自行合成的芳基甘氨酰胺的手性拆分。以高硫酸化 β 环糊精为手性选择剂 ,在中性而不是常用的强酸性条件下 ,于 6min内基线拆分了全部芳基甘氨酰胺。考察了高硫酸化 β 环糊精浓度、缓冲液类型及浓度、有机添加剂及其含量等对拆分的影响 ,得到优选拆分体系组成为 :1 5g/L高硫酸化 β 环糊精 ,0或 1 0 % (体积分数 )甲醇 ,2 0mmol/L 3 (N 吗啡啉 )丙磺酸 ,pH 6 5。 9种芳基甘氨酰胺的 D 构型均先于 L 构型出峰 ,初步讨论了芳基甘氨酰胺结构与出峰顺序的关系。     

毛细管电泳手性拆分美托洛尔、阿普洛尔和卡替洛尔对映体

提出了毛细管电泳手性拆分β-受体阻滞剂美托洛尔、阿普洛尔、卡替洛尔的方法。考察手性拆分剂的种类及浓度、缓冲溶液的浓度及pH对手性拆分的影响。在95mmol.L-1Tris-H3PO4缓冲溶液中添加15mmol.L-1羟丙基-β-环糊精(HP-β-CD)和5g.L-1羧甲基-β-环糊精(CM-β-CD),美托洛尔对映体和阿普洛尔对映体分别在pH3.2和pH3.8获得基线分离,卡替洛尔对映体在同一分离条件下在pH3.8获得较好分离,分离度达1.0。     

离子液体作为添加剂的毛细管电泳法拆分盐酸金刚乙胺

将新离子液体[EIMCH2CONHBu]BF4用于毛细管电泳法拆分手性药物,建立了以β-环糊精为手性选择剂拆分盐酸金刚乙胺对映体的毛细管电泳方法。分别考察了离子液体浓度,手性选择剂浓度,缓冲溶液种类、浓度及pH值,分离电压等参数对分离度的影响,从而确定了盐酸金刚乙胺对映体的最佳拆分条件:[EIMCH2CONHBu]BF4溶液体积分数3.2%,β-环糊精18 mmol/L,NaH2PO4 15 mmol/L,缓冲液pH 3.03,分离电压15 kV。在优化的实验条件下,盐酸金刚乙胺对映体得到基线分离,分离度可达1.51。实验结果表明[EIMCH2CONHBu]BF4能够增强β-环糊精的手性拆分能力,对手性拆分有协同作用。     

毛细管电泳技术对手性药物西酞普兰的拆分方法研究

利用手性试剂磺化β-环糊精(S-β-CD),建立了对药物西酞普兰的毛细管电泳(CE)拆分方法。实验考察了背景电解液(BGE)组成及浓度、pH值、手性拆分试剂种类及其浓度对拆分结果的影响。优化后的分离条件为:BGE采用20 mmol/L柠檬酸+0.04%S-β-CD(pH=5.50),采用压力进样0.5psi、5s,分离电压为+20kV,紫外检测波长为205nm。结果表明:CE对西酞普兰的两个对映体的检出限均为90μg/L,迁移时间和峰面积的相对标准偏差(RSD)都低于3.0%(n=5),在0.05~100mg/L范围内有良好的线性关系,其线性相关系数(R2)都大于0.998。该方法可成功用于商品药物来士普的质量检测,回收率在103%~108%之间。     

MAH-β-CD的合成及其在毛细管电泳手性拆分中的应用

合成了顺丁烯二酸酐-β-环糊精(MAH-β-CD),并通过红外光谱、质谱对其结构进行表征。以20 mmol/L乙酸铵为缓冲溶液,MAH-β-CD作为手性选择剂,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。考察了缓冲溶液pH、分离电压和手性选择剂浓度等对拆分效果的影响,在优化条件下,成功拆分了3种氨基酸(DL-甲硫氨酸、DL-精氨酸、DL-赖氨酸)和两种手性药物(沙丁胺醇、氯美扎酮)对映体,分离度分别为5.11,5.55,2.99,2.33和1.64。     

应用四甲基氢氧化铵控制电渗流的毛细管电泳方法分离多沙唑嗪及其中间体的对映体

建立了毛细管电泳手性分离多沙唑嗪中间体对映体的方法,并同时分离了多沙唑嗪对映体。考察了不同种类季铵盐对电渗流及分离的影响,其中四甲基氢氧化铵(TMB)能有效控制电渗流并提高组分的分离度。实验还考察了其他因素,如pH值、分离电压和磷酸二氢钠浓度对分离的影响。所用的毛细管为40 cm(有效长度30 cm)×50 μm,缓冲液为12 mmol/L β-环糊精、30 mmol/L TMB、60 mmol/L 磷酸二氢钠(pH 2.2),分离电压为20 kV。在此条件下多沙唑嗪及其中间体的对映体均达到了基线分离。实验结果表明,一些用β-环糊精不能完全分离的对映体通过加入TMB控制电渗流能达到满意的分离效果。     

毛细管电泳/非接触式电导法分离检测手性药物氨氯地平对映体

采用毛细管电泳/电容耦合非接触式电导( CE/C4 D),以18 mmol/L柠檬酸+6 mmol/L氨水+12 mg/L羟丙基甲基纤维素(HPMC)+ 35 mmol/L羟丙基-β-环糊精(HP-β-CD)为电泳运行液,熔融石英毛细管(50μm i.d.×45 cm,leff=40 cm),正高压(+15 kV)分离...     

Enantiomeric separation of a group of chiral dihydropyridines by electrokinetic chromatography

Electrokinetic chromatography (EKC) was employed to achieve the enantiomeric separation of a group of chiral 1,4-dihydropyridines (DHPs) with pharmacological activity. Micelles of bile salts alone or mixed with neutral cyclodextrins, micelles of sodium dodecyl sulfate (SDS) mixed with neutral cyclodextrins, and anionic cyclodextrin derivatives, i.e., carboxymethyl-gamma-cyclodextrin (CM-gamma-CD), carboxymethyl-beta-cyclodextrin (CM-beta-CD), and succinylated beta-cyclodextrin (Succ-beta-CD), were employed as pseudostationary phases. The enantiomeric separation ability of these chiral selectors with respect to DHPs was studied in different experimental conditions. CM-beta-CD was shown to be the best chiral selector to perform the enantiomeric separation of DHPs by EKC. Next, the influence of the CM-beta-CD concentration, the pH and nature of the buffer, the temperature, and the applied voltage on the enantiomeric resolution of DHPs was studied. The use of a 50 mM ammonium acetate buffer, pH 6.7, 25 mM in CM-beta-CD together with an applied voltage of 15 or 20 kV, and a temperature of 15 degrees C enabled the individual enantiomeric separation of twelve DHPs, each one into its two enantiomers, and their separation in multicomponent mixtures of up to six DHPs into all their enantiomers.     

Enatiomeric analysis of simendan by CE with beta-CD as chiral selector compared with CMPA-HPLC

The chiral separation of simendan enantiomers using capillary electrophoresis was studied with beta-cyclodextrin (beta-CD) as chiral selector. The influences of the concentration and pH of borate buffer solution, beta-CD concentration and methanol content in the background electrolyte were investigated. These factors were compared with those in an HPLC with beta-CD as chiral mobile phase additive (CMPA-HPLC). The quantification properties of the developed CE method were examined. A baseline separation of simendan enantiomers was achieved in the background electrolyte of 20 mmol/L borate buffer (pH 11.0) containing 12 mmol/L beta-CD-methanol (50:50 in volume ratio). The CE method is comparable with CMPA-HPLC in chiral resolution, although the optimal pH in CE (11.0) is much higher than that (6.0) in CMPA-HPLC. This chiral CE method is applicable to the quantitative ananlysis and enantiomeric excess value determination of L-simendan.     

Enantioselective separation of the sunscreen agent 3-(4-methylbenzylidene)-camphor by electrokinetic chromatography: Quantitative analysis in cosmetic formulations

3-(4-Methylbenzylidene)-camphor (MBC) is a chiral sunscreen agent used in cosmetic products. In this work, the enantioseparation of MBC has been performed by EKC and applied to the analysis of the MBC enantiomers in cosmetic creams. Different experimental conditions (type and concentration of the chiral selector, temperature, and sample solvent) have been optimized. Due to the neutral nature of this compound, anionic CD derivatives were investigated as chiral selectors. Carboxymethylated-beta-CD (CM-beta-CD) showed the highest chiral separation power, observing that a 15 mM concentration of this CD at a working temperature of 15 degrees C enabled to obtain the highest enantioresolution. However, under these conditions, tailing of peaks obtained for the enantiomers was observed. The addition of increasing concentrations of the neutral alpha-CD to CM-beta-CD at a 15 mM concentration in a 100 mM borate buffer at pH 9.0 improved the enantiomeric separation and decreased peak tailing. The use of DMF for the total dissolution of the cosmetic creams, and methanol:water (1:1 v/v) for appropriate dilution enabled to observe good shape and size for the peaks of the MBC enantiomers. After optimizing a method for the preconditioning of the capillary, the analytical characteristics of the chiral separation method for the analysis of MBC were investigated. Linearity, LODs and LOQs, precision (instrumental repeatability, method repeatability, intermediate precision), accuracy, and selectivity were evaluated. The method was applied to analyze MBC enantiomers contained in two commercial cosmetic creams containing racemic MBC and to study the skin absorption of this compound with time.     

毛细管区带电泳法拆分匹伐他汀钙对映体

建立了匹伐他汀钙对映体的毛细管区带电泳(CZE)拆分方法。分别考察了电泳电压,缓冲溶液种类、浓度及pH值,环糊精种类及浓度,添加剂种类及浓度等参数对实验结果的影响,从而确定了匹伐他汀钙对映体的最佳拆分条件: 电泳电压为18 kV;运行缓冲溶液为80 mmol/L的Tris-HCl缓冲体系,pH值为3.20,其中含有50 mmol/L HP-β-CD(羟丙基-β-环糊精)和5 mmol/L SDS(十二烷基磺酸钠);采用重力进样,进样高度17 cm,进样时间为2 s。在优化的实验条件下,匹伐他汀钙对映体得到了较好的分离,分离度可达2.17。实验结果表明该方法可用于匹伐他汀钙对映体的分离,具有快速、便捷、准确性好等优点。     

肝糖选择剂-毛细管电泳手性拆分盐酸度洛西汀对映体及分离机制

以肝糖为毛细管电泳手性选择剂,对盐酸度洛西汀对映体的分离进行研究,建立了拆分方法.考察了手性选择剂浓度、运行缓冲液的离子强度、pH值及分离电压对手性分离的影响.在3.0% (m/V)肝糖、50 mmol/L Tris-H3PO4(pH 3.0)的运行缓冲液中,分离电压25 kV时,盐酸度洛西汀两对映体分离度达1.84.对分离机制进行了初步探讨.     

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。     

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.     

Separation of ritalin racemate and its by-product racemates by capillary electrophoresis

Ritalin, [(+)-threo]methylphenidate hydrochloride, is a chiral drug substance with two chiral centers. The drug substance may contain three pairs of enantiomers, [(+)-threo], [(-)-threo], [(+)-erythro] and [(-)-erythro] isomers, and its degradation products, threoritalinic acid racemate. Determination of the optical purity of ritalin drug substance and the amount of its by-product isomers is a critical step in the single-isomer drug development. In order to efficiently recognize the three pairs of enantiomers by one method, capillary electrophoresis (CE) was employed for the separation. The three pairs of enantiomers in CE showed different enantioselectivities with eight different types of CDs. Only 2,6-di-o-methyl-beta-cyclodextrin (DM-beta-CD) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) showed enantioselectivity to all these pairs of enantiomers. With respect to separation resolution and efficiency, DM-beta-CD was chosen as the chiral selector. For optimization of the separation conditions, the concentration of DM-beta-CD, pH of the buffer solution, and temperature of the capillary were further studied.