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。     

高效毛细管电泳同时拆分外消旋头孢他啶及头孢曲松钠

用毛细管电泳β－环糊精（β－CD）添加剂法同时拆分外消旋头孢他啶及头孢曲松钠，主要考察了影响分离和测定的因素：（β－CD浓度，背景电解质的pH值，分离电压和毛细管的柱温。通过优化得到了毛细管电泳手性分离头孢他啶及头孢曲松钠对映体的实验方法，在280nm处进行紫外检测，分离温度为25℃，压力进样6s，分离电压为28kV，背景缓冲液含50mmol/L磷酸二氢钠、0.4mmol/Lβ－环糊精（β-CD）、3.0mmol/L（三羟甲基）氨基甲烷（Tirs),pH为7.15的条件下，头孢他啶及头孢曲松钠同时能达到基线分离。对其拆分机理进行了探讨。     

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.     

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。     

西他沙星差向异构体的毛细管电泳分离

以γ-环糊精和D-苯丙氨酸为手性选择剂,采用毛细管区带电泳成功地分离了新型抗菌素西他沙星差向异构体。考察了添加剂的种类、浓度和缓冲溶液的pH对毛细管电泳分离西他沙星的影响。分离电压为15 kV,选用60 cm(有效长度52.5 cm)×50 μm i.d.的石英毛细管,缓冲溶液组成为10 mmol/L KH2PO4-K2HPO4(pH 4.5),10 mmol/L CuSO4,20 mmol/L γ-环糊精和 10 mmol/L D-苯丙氨酸。实验结果表明,添加剂的种类和浓度是影响西他沙星手性分离的重要因素,只有当 D-苯丙氨酸、铜离子和γ-环糊精同时存在并达到一定浓度时,西他沙星差向异构体在毛细管电泳中才具有良好的分离效果。该方法可用于西他沙星差向异构体的定量分析。     

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。     

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.     

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。     

阿苯达唑亚砜对映异构体的高效毛细管电泳手性拆分

建立了高效毛细管电泳拆分阿苯达唑亚砜对映体的方法，考察了背景电解质pH、环糊精种类和浓度，有机改性剂种类和浓度对分离的影响，对分离条件进行了优化。实验结果表明：在含36g/L磺化β－环糊精和10％甲醇的20mmol/L Tris-H3PO4(pH2.5）缓冲体系中，阿苯达唑亚砜对映体具有良好的分离效果。     

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。     

毛细管电泳法手性拆分合成药物氨氯地平及其中间体

 建立了毛细管电泳手性拆分氨氯地平药物中间体的方法 ,并同时拆分了氨氯地平。考察了不同手性拆分试剂对手性选择性的影响 ,其中羧甲基 β 环糊精 (CM β CD)能够给出满意的拆分结果。在以CM β CD为手性拆分试剂的基础上 ,还考察了各种因素诸如流动相的pH值、环糊精的浓度以及电压对分离的影响。最佳拆分条件为 :30mmol/L磷酸盐 +5 0mmol/LCM β CD(pH 6 12 )。在此条件下 ,药物中间体及氨氯地平的分离度分别为 1 5 5和 1 73,结果令人满意。     

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.     

Enantiomer separation of miconazole by capillary electrophoresis with dual cyclodextrin systems.

A cyclodextrin-modified micellar capillary electrophoretic method (MECC) was developed using mixtures of beta, cyclodextrins (beta-CD) and mono-3-O-phenylcarbamoyl-beta-CD as chiral additives for the chiral separation of miconazole with the dual CDs systems. The enantiomers were resolved using a running buffer of 50 mmol/L borate pH 9.5 containing 15 mmol/L beta-CD and 15 mmol/L mono-3-O-phenylcarbamoyl-beta-CD containing 50 mmol/L sodium dodecyl sulfate and 1 mol/L urea. A study of the respective influence of the beta-CD and the mono-3-O-phenylcarbamoyl-beta-CD concentration was performed to determine the optimal conditions with respect to the resolution. Good repeatability of the method was obtained.     

毛细管区带电泳法拆分手性药物萘普生和氟联苯丙酸

 70-72 -------------------------------------------------------------------------------- 以β-环糊精(CD)作为手性选择剂 ,用毛细管区带电泳法成功地拆分了两种弱酸性药物萘普生(naproxen)和氟联苯丙酸(flurb iprofen),并比较了4种环糊精［β-环糊精(β-CD)、二甲基-β-环糊精( DM-β-CD)、羟丙基-β-环糊精(HP-β-CD)和三甲基-β-环糊精( TM-β-CD)］对手性拆分的影响,同时测定了萘普生对映体在不同环糊精中的出峰次 序。通过实验,发现对于此类化合物拆分的最佳pH值为5左右,即接近于该类化合物的pK a值。该方法适用于酸性手性药物的拆分。     

高效液相色谱手性流动相添加法拆分奥昔布宁对映体

采用C18固定相,以羟丙基-β-环糊精为手性流动相添加剂,建立了奥昔布宁对映体的高效液相色谱拆分方法。考察了手性添加剂、有机极性调节剂、缓冲盐的种类和浓度以及流动相的pH值和流速及柱温等因素对对映体分离的影响。在最佳分离条件下,奥昔布宁对映体的分离度为1.54,检测限为1.0 ng。该方法简便,重复性好,比手性固定相法更加经济。     

Separation and migration behavior of structurally related phenothiazines in cyclodextrin-modified capillary zone electrophoresis

The influences of buffer pH and the concentration of beta-cyclodextrins (beta-CDs) on the separation and migration behavior of 13 structurally related phenothiazines in CD-modified capillary zone electrophoresis (CD-CZE) using a phosphate background electrolyte at low pH were investigated. We focused on the separation of these phenothiazines, including the enantiomers of chiral analytes, with the use of beta-CD and hydroxypropyl-beta-CD (HP-beta-CD) as electrolyte modifiers or chiral selectors at concentrations less than 8 mM. The results indicate that the interactions of phenothiazines with beta-CDs are very strong and that effective separations of 13 analytes can be achieved with addition of 0.3 mM beta-CD or 0.5 mM HP-beta-CD in a phosphate buffer at pH 3.0. Binding constants of phenothiazines to beta-CDs were evaluated for a better understanding of the interactions of phenothiazines with beta-CDs.     

Influence of buffer substances and urea on the beta-cyclodextrin-mediated chiral separation of dipeptides in CE

The influence of buffering substances and urea on the beta-CD-mediated chiral separations of the dipeptides Ala-Phe and Ala-Tyr was studied in the pH range of 2.5-3.8. Only minor effects of the buffer substances on the chiral separation selectivity alpha were observed at a beta-CD concentration of 15 mg/mL. In contrast, the selectivity improved at pH 2.5 but decreased at pH 3.8 upon the addition of 2 M urea. Complexation by beta-CD resulted in a shift of the pK(a) values toward higher values which was more pronounced for the DD-enantiomers of both dipeptides than for the LL-enantiomers. Addition of urea further increased the pK(a) shift. The consequence of this pK(a) shift is an increase of the fraction of the protonated, positively charged form of the peptides which explained the improved chiral separation at pH 2.5 and the reduced selectivity at pH 3.8. A pK(a) shift by the addition of urea was also observed for N-tert-butyloxycarbonyl phenylalanine (BOC-Phe) as a model compound that is strongly complexed by beta-CD. This effect was not stereospecific. Addition of urea resulted in a decrease of the apparent complexation constants between beta-CD and the BOC-Phe enantiomers to the same extent but this did not affect the separation selectivity alpha. For chiral separations that display strong pH dependence such as peptide enantioseparations close to the pK(a) values of the compounds, urea may not solely be regarded as a solubility enhancer for beta-CD but may also influence the separation.     

2-O-(2-hydroxybutyl)-beta-cyclodextrin as a chiral selector for the capillary electrophoretic separation of chiral drugs.

A new beta-cyclodextrin (beta-CD) derivative, 2-O-(2-hydroxybutyl)-beta-CD (HB-beta-CD), was successfully synthesized and used as chiral selector in capillary zone electrophoresis. Six chiral drugs, such as anisodamine, ketoconazole, propranolol, promethazine, adrenaline and chlorphenamine enantiomers, belonging to different classes of compounds of pharmaceutical interest were resolved. The chiral resolution (R(S)) was strongly influenced by the concentrations of the cyclodextrin derivative, the background electrolyte, and the pH of the background electrolyte. Under the conditions of 50 mmol/L tris-phosphate buffer at pH 2.5 containing 5 mmol/L 2-O-(2-hydroxybutyl)-beta-CD, the baseline separation of enantiomers, such as anisodamine (R(S) = 3.10), ketoconazole (R(S) = 3.01), propranolol (R(S) = 3.87), promethazine (R(S) = 3.63), adrenaline (R(S) = 3.42) and chlorphenamine (R(S) = 2.96), could be achieved.     

5-(对-羟基苯基):-5-苯基乙内酰脲的反相高效液相手性分离测定法

以β－ＣＤ为手性流动相添加剂、苯巴比妥为内标,于ＦＬＣ－Ｃ８反相柱上建立了鼠肝微粒体中５－（对－羟基苯基）－５－苯基乙内酰脲（ｐ－ＨＰＰＨ）外消旋体的拆分方法。测得ｐ－ＨＰＰＨ对映体的线性范围为０．５～１１０ｍｇ／Ｌ（ｒ＝０．９９９６）;最低检出量为５ｎｇ（Ｓ／Ｎ＝３）;Ｓ－ｐ－ＨＰＰＨ的回收率为９３．６％±２．８％,Ｒ－ｐ－ＨＰＰＨ的回收率为９４．７％±１．８％;日内和日间精密度ＲＳＤ值均小于２％。所建立的方法具有结果准确、操作方便等特点。     

Enantiomeric separation of citalopram and its metabolites by capillary electrophoresis

A simple and fast capillary electrophoretic method has been developed for the enantioselective separation of citalopram and its main metabolites, namely N-desmethylcitalopram and N,N-didesmethylcitalopram, using beta-cyclodextrin (beta-CD) sulfate as the chiral selector. For method optimisation several parameters were investigated, such as CD and buffer concentration, buffer pH, and capillary temperature. Baseline enantioseparation of the racemic compounds was achieved in less than 6 min using a fused-silica capillary, filled with a background electrolyte consisting of a 35 mM phosphate buffer at pH 2.5 supplemented with 1% w/v beta-CD sulfate and 0.05% w/v beta-CD at 25 degrees C and applying a voltage of -20 kV. A fast separation method for citalopram was also optimized and applied to the analysis of pharmaceutical formulations. Racemic citalopram was resolved in its enantiomers in less than 1.5 min using short-end injection (8.5 cm, effective length) running the experiments in a background electrolyte composed of a 25 mM citrate buffer at pH 5.5 and 0.04% w/v beta-CD sulfate at a temperature of 10 degrees C.