超临界流体色谱法拆分萘普生对映体

目的:建立拆分萘普生对映体的方法。方法:采用超临界流体色谱法。以萘普生对映体的分离时间、容量因子、分离因子、分离度为考察指标,优选手性色谱柱、流动相中极性添加剂种类及占比、背压和柱温的条件。结果:优选条件为手性色谱柱采用CHIRALPAK®AD-H,极性添加剂为异丙醇(占比为20%),背压170 bar,柱温20℃,检测波长283 nm。在此条件下萘普生对映体能够达到基线分离,分离度为4.31,分离因子为1.90,且精密度、稳定性和重复性试验中相关指标的RSD均≤2.65%(n=5)。结论:建立的拆分方法简单、重现性好、拆分效果好,可用于萘普生对映体的手性分离。     

键合型多糖手性固定相超临界流体色谱用于取代苯基哌嗪衍生物的拆分(英文)

合成了六个新型的1-取代苯基-4-[3-(吲哚-4-氧基)-2-羟丙基]-哌嗪消旋体化合物1–6,并利用键合型多糖手性固定相超临界流体色谱完成了对其的手性拆分研究。实验表明,基于固定相Chiralpak ⅠA的拆分优于其它两种键合型固定相(Chiralpak ⅠB、Chiralpak ⅠC),改性剂异丙醇的效果优于乙醇、甲醇、四氢呋喃、乙腈、二氯甲烷。本文还研究了有机改性剂、背压与柱温对六个化合物对映体拆分的影响。结果表明,改性剂组成最大程度地影响了分离时间,柱温的改变对分离时间的影响较小但最大程度地影响了对映体选择性的变化。最优的拆分条件为:固定相为Chiralpak ⅠA柱,柱温为35℃,背压为120bar,流动相为35%异丙醇(含0.1%二乙胺),流速为3.0mL/min,紫外检测波长为283nm。该六个消旋体化合物在10分钟内得到了良好的拆分。超临界流体色谱法是拆分该类化合物对映体的有效方法。     

超临界流体色谱法拆分奈必洛尔关键手性中间体

目的 建立奈必洛尔关键手性中间体6-氟-3,4-二氢2H-1-苯并吡喃-2-甲酸的超临界流体色谱法（SFC）。方法 采用分析型超临界流体色谱法结合大赛璐Chiralpak IG（4.6 mm ´150 mm, 5 µm）手性色谱柱直接拆分该手性中间体，分别考察了固定相的种类、改性剂的种类及比例、流速、温度和背压等因素对手性分离的影响。结果 建立了分析型的色谱拆分条件：流动相为超临界CO2-甲醇（75:25, V/V），流速为2.0 mL·min^-1，检测波长为220 nm；柱温为350 K，背压为100 bar。结论 该方法对映体分离度好（4.22），保留时间短，适合分析及制备放大。     

直链淀粉手性固定相拆分咪康唑对映体

目的使用Chiralpak AD-H手性色谱柱,建立咪康唑的HPLC对映体拆分方法。方法考察流动相中有机改性剂种类和浓度、流速、柱温等因素对对映体分离的影响。结果当流动相为正己烷-乙醇(体积比为90∶10)、流速为0.6 mL.min-1、温度为25℃时,对映体在Chiralpak AD-H柱上分离效果最佳。结论该方法适于咪康唑对映体的分离分析。     

手性固定相高效液相色谱法拆分雌马酚对映体

目的:建立手性固定相拆分雌马酚的高效液相色谱方法。方法:采用Daicel公司Chiralcel OJ-H(250 mm×4.6 mm,5.0μm,)手性色谱柱拆分雌马酚对映体,考察流动相中异丙醇比例、柱温、流速对分离效果的影响。确定了较佳的拆分条件:以正己烷-异丙醇(75∶25)为流动相,流速为1.0 mL.min-1,检测波长280 nm,柱温30℃。结果:Chiralcel OJ-H色谱柱能使雌马酚对映体达到基线分离,分离度达3.26,(S)-对映体先于(R)-对映体出峰。结论:本法操作简便,重复性好,可用于雌马酚对映体的分离和质量控制。     

α_1酸性糖蛋白柱拆分西布曲明对映体

目的以α1酸性糖蛋白为固定相,建立了西布曲明的HPLC对映体拆分方法。方法考察了有机改性剂种类、比例、缓冲盐浓度、pH值、柱温以及流速等因素对西布曲明对映体拆分的影响,并对拆分机理进行了探讨。结果优化实验条件后,分离西布曲明的最佳色谱条件:流动相为异丙醇20 mmol.L-1NH4Ac(pH 5.0)(体积比为6∶94),柱温为20℃,流速为0.6 mL.min-1,在223 nm下检测。结论西布曲明对映体在α1酸性糖蛋白柱上能被完全分离。     

手性固定相NP-HPLC法拆分比卡鲁胺对映体

建立了正相色谱法拆分比卡鲁胺对映体.考察了色谱柱、流动相中异丙醇浓度、流速和温度对对映体拆分的影响,确定拆分条件如下:采用Chiralpak AD-H手性固定相,以正己烷-异丙醇(70:30)为流动相,检测波长270 nm,流速0.6 ml/min,柱温20℃.在此条件下,比卡鲁胺对映体分离完全,分离度为7.0.     

α_1-酸性糖蛋白柱拆分布洛芬对映体

目的使用α1 酸性糖蛋白手性固定相 (α1 AGP)拆分布洛芬对映体。方法分别以异丙醇、甲醇、乙腈为有机改性剂 ,考察了有机改性剂的种类、浓度、磷酸盐缓冲液的 pH值及流速对对映体拆分的影响。结果布洛芬对映体在AGP柱上的最佳分离条件是 :流动相为甲醇 10mmol·L-1磷酸盐缓冲液 (V∶V =1∶99,pH7 0 ) ,流速为 0 3mL·min-1,柱温 30℃。结论布洛芬对映体可以在AGP固定相上得到完全分离。     

萘普生对映体的手性分离和纯度检查

目的:建立萘普生手性分离和光学纯度检查的高效液相色谱方法。方法:采用Chiralpak AD-H(4.6 mm×250 mm,5μm,Daicel公司)手性色谱柱在正相条件下拆分萘普生对映体,考察了固定相种类、流动相组成、柱温及流速等对萘普生对映体分离的影响,流动相为正己烷-异丙醇(30∶70,v/v),检测波长272 nm,流速0.5 mL.min-1,柱温20℃。结果:在此条件下,萘普生及其(R)-(-)-构型体达到基线分离,分离度为3.3。结论:该法简单快速,重现性好,能够用于萘普生对映体的分离和纯度考察。     

手性固定相高效液相色谱法拆分佐米曲普坦对映体

目的 以纤维素氨基甲酸脂作为手性固定相,研究佐米曲普坦的高效液相色谱手性拆分方法.方法 对流动相的比例、柱温以及流速等进行了优化.采用Chiralcel OD柱(250mm×4.6mm,5μm),以正已烷-异丙醇-三乙胺(85∶15:0.2,v/v)为流动相,流速为0.7ml·min-1,检测波长280nm,柱温30℃.结果 用Chiralcel OD手性柱在拟定的色谱条件下可实现佐米曲普坦对映体的完全分离,分离度为1.6.R-(-)型先于S-( )型出峰.结论 流动相中异丙醇的含量由低向高变化时,有降低分离度的趋势;在流动相中增大三乙胺的比例对拆分较为有利;温度较高时,有利于对映体的分离;较低的流速可改善分离度,但会延长对映体的出峰时间.     

3种新型α1-受体阻断剂的手性流动相HPLC分离与制备

目的建立3种新型α₁-受体阻断剂的手性流动相HPLC分离与半制备方法。方法通过探讨有机相、手性添加剂、流动相的pH、扫尾剂、反相固定相对手性分离的影响,选择最佳的手性分离条件。结果基线分离了3种新型α₁-受体阻断剂对映体,并制备了毫克级样品。结论所建立的分离与制备方法可用于该类新药的手性研究与开发。     

Exploration of liquid and supercritical fluid chromatographic chiral separation and purification of Nutlin-3--a small molecule antagonist of MDM2

Inhibition of the MDM2–p53 interaction can stabilize the p53 protein and offer a novel strategy for cancer therapy. The imidazoline compound (Nutlin-3) is a promising small molecule antagonist of the MDM2–p53 interaction. This compound was synthesized as a racemic mixture, and one enantiomer is 100–200-fold more active than the other enantiomer. In this study, various enantiomeric separation approaches were explored to resolve the Nutlin-3 enantiomers using chiral supercritical fluid chromatography (SFC) as well as chiral liquid chromatography (LC) under normal phase mode, reversed phase mode and polar organic phase mode. The chiral SFC method based on Chiralcel OD column showed superior separation in terms of selectivity and efficiency. Optimization of the chiral separation method enabled high throughput preparative scale purification. Ultimately, 5 g of racemic mixture were purified on Prep-SFC in 75 min with the recovery rate above 92%.     

High performance liquid chromatographic separation of eight drugs collected in Chinese Pharmacopoeia 2010 on amylose ramification chiral stationary phase

The enantiomers separation of eight pharmaceutical racemates collected in Chinese Pharmacopoeia 2010 (Ch.P2010), including nitrendipine, felodipine, omeprazole, praziquantel, sulpiride, clenbuterol hydrochloride, verapamil hydrochloride and chlorphenamine maleate, was performed on chiral stationary phase of amylose ramification by high performance liquid chromatography (HPLC) on Chiralpak AD-H column and Chiralpak AS-H column with the mobile phase consisted of isopropanol and n-hexane. The detection wavelength and the flow rate were set at 254 nm and 0.7 mL/min, respectively. The effects of proportion of organic additives, alcohol displacer and temperature on the separation were investigated. The results indicated that eight chiral drugs were separated on chiral stationary phase of amylase ramification in normal phase chromatographic system. The chromatographic retention and resolution of enantiomers were adjusted by factors, including the changes of the concentration of alcohol displacer in mobile phase, organic alkaline modifier and column temperature. It was shown that the resolution was improved with reducing concentration of alcohol displacer. When the concentration of organic alkaline modifier was 0.2%, the resolution and the peak shape were fairly good. Most racemates mentioned above had the best resolution at column temperature of 25 °C. The best temperature should be kept unchanged in the process of separation so as to obtain stable separation results.     

高效液相色谱用Pirkle型手性柱直接拆分阿折地平(英文)

本文使用Pirkle型Sumichiral OA-2500手性柱,研究了正相和反相色谱直接分离阿折地平对映体的流动相条件。使用正相体系,阿折地平在正己烷–乙醇(90:10,v/v)流动相条件下获得了很好的分离(分离度Rs达到4.0),而使用推荐的流动相正己烷–乙醇(60:40,v/v),则可以在更短的13分钟内获得分离(分离度Rs为2.7)。使用反相的甲醇和含有0.05mol/L醋酸铵的甲醇做流动相,仅能获得部分分离。用同样的实验条件研究了氨氯地平和尼莫地平的拆分,并在正相条件下获得了部分分离。     

Chiral separation of potent corticotropin-releasing factor-1 receptor antagonists by supercritical fluid chromatography

Pyrazinones bearing an N-1-alkyl chain with a chiral center have been reported as potent antagonists of the corticotropin-releasing factor-1 receptor (CRF1R). Separation of individual enantiomers for preclinical testing was an important aspect of lead optimization. To evaluate the applicability and efficiency of supercritical fluid chromatography (SFC) for enantiomeric resolution of this class of compounds, enantiomeric pairs of eight pyrazinones with different structural characteristics were tested under an array of SFC conditions. The results showed that pyrazinones with a 1-cyclopropyl-2-methoxyethyl substituent were readily separated with a Chiralpak AD-H or Chiralcel OD-H column with ethanol as the modifier. On the other hand, analogs with a less polar alkyl substituent were not amenable to the general method and required further optimization of the chromatographic conditions. In addition, structural variations on the pyrazinone core and aromatic moiety had an impact on the chiral resolution of this class of compounds. This investigation led to the development of efficient chiral SFC methods for separating all eight pyrazinone enantiomeric pairs encompassing an array of structural variations.     

Chiral separation of cefadroxil by capillary electrochromatography

In this paper, the chiral separation of cefadroxil was studied by capillary electrochromatography. Monolithic capillary column was prepared for the separation of cefadroxil enantiomers. The optimum buffer contained 28.5 mmol/L sodium acetate, 0.95% (v/v) acetic acid, 19 mmol/L beta-cyclodextrin (beta-CD) and 5% (v/v) isopropanol in formamide solution (pH 7.0), with the running voltage of 12 kV, the UV detector wavelength of 254 nm, the sample injected time of 8s and the temperature of 25 degrees C. Under these conditions, the column efficiency of cefadroxil enantiomers were N1=5324 and N2=23,768 with a selectivity factor (alpha) of 1.056 and resolution (Rs) of 0.978. The effect of buffer pH value, beta-CD concentration, organic modifier (isopropanol) concentration and voltage was also investigated for the separation by CEC.     

NP-HPLC法拆分特拉唑嗪对映体

建立了正相高效液相色谱法拆分特拉唑嗪对映体.采用Chiralpak AD-H手性色谱柱,考察了流动相组成、流速及柱温对对映体分离的影响.确定最佳拆分条件:流动相为正己烷-异丙醇-二乙胺(65∶35∶0.1),流速0.7 ml/min,检测波长254 nm,柱温25℃.在此条件下特拉唑嗪对映体的分离度为3.1.两对映体在2.5～7.5 μg/ml浓度范围内线性关系良好,平均回收率为99.8％和99.4％,RSD为0.44％和0.42％.     

HPLC万古霉素手性柱和手性流动相添加剂法分离酮洛芬对映体

目的以万古霉素为手性选择子,建立酮洛芬对映体以手性柱法和流动相添加剂法进行手性分析的方法。方法考察万古霉素用量、有机改性剂用量及缓冲液pH值对酮洛芬对映体手性拆分的影响,并进行了定量分析的方法验证。结果两种拆分方法都使酮洛芬对映体达到了基线分离,都适合于酮洛芬对映体的定性和定量分析。结论所建立的两种方法均可用于S-(+)-酮洛芬的光学纯度检测。     

高效毛细管电泳法拆分氧氟沙星对映体的研究

用牛血清白蛋白为手性选择剂,异丙醇为修饰剂,应用毛细管电泳法拆分氧氟沙星对映体,实验时柱温为30℃,电泳电压15kV,采用50mg·ml^-1牛血清白蛋白—5%异丙醇—磷酸盐缓冲液(pH6.0)为电泳电解液,检测波长为293nm,得到了良好拆分结果。左、右旋成分迁移时间及峰面积的RSD分别为1.6%,1.8%和1.1%,2.8%。应用于氧氟沙星产品研究,其左、右旋成分峰面积比值为0.995～0.998,RSD为1.8%～2.0%。并研究了pH值、牛血清白蛋白浓度、异丙醇浓度、柱温、电泳电压对对映体迁移时间及分辨率的影响,方法简便快速。