手性药物的色谱分离方法

综述了手性药物常用的色谱分离方法，如气相色谱、高效液相色普、高效毛细管电泳色谱及超临界流体色谱等在手性药物扩分研究中的应用及近年来的研究进展。     

色谱法拆分手性药物在我国的应用

目的:为药物研发及质量控制提供参考。方法:根据文献,综述了色谱法拆分手性药物的主要分类、方法及其应用。结果与结论:色谱法拆分药物对映体一般分为直接法和间接法。主要方法包括薄层色谱(TLC)、高效液相色谱(HPLC)、气相色谱(GC)、超临界流体色谱(SFC)和毛细管电泳(CE)法等。能用于TLC法的手性载体很少;HPLC法是目前的常用方法,但手性固定相的成本太高,手性流动相添加剂使色谱条件复杂化;GC法对药物的沸点要求严格,且非对映体制备困难,应用有限;SFC法正处于迅速发展阶段,具有检测方式和固定相种类多样等特点,将在手性药物分离、分析等方面发挥重大作用;CE法在手性拆分中显示了兼有高压电泳的高速、高分辨率及HPLC的高效率的优点,但适用的手性固定相不多。随着各种分离原理、方法的深入研究以及色谱联用技术的不断完善,色谱法在手性药物拆分中将会发挥越来越重要的作用。     

超临界流体色谱在药物分析中的研究进展

超临界流体色谱是以超临界流体为流动相,依靠流动相的溶剂化能力来进行分离分析的一种色谱,具有分离速度快、效能高、绿色环保等优点,是气相色谱和液相色谱的有力补充,具有广阔的应用前景。本文利用中国知网（CNKI）、ScienceDirect、PubMed等数据库检索了近几年来超临界流体色谱在药物分析中的研究文献,归纳了其在手性药物、天然产物、药物代谢和杂质检测中的应用进展,并对今后的进一步研究提出思考。     

色谱手性固定相在手性药物拆分中的应用

色谱手性固定相（chiral stationary phases，CSPs）在手性药物分析和制备拆分中具有很重要的作用。本研究对5种带有CSPs的手性色谱技术以及在高效液相色谱（high performance liquid chromatography，HPLC）和超临界流体色谱（supereritical fluid chromatography，SFC）中CSPs的4种流动相模式和6种类型进行了综述，提出了CSPs色谱柱的筛选策略，并讨论了手性药物拆分从分析到制备的转变。     

手性药物拆分的研究进展

目前，利用酶法、超临界流体色谱法、化学法、高效液相色谱法、气相色谱法、毛细管电泳法和分子烙印法拆分药物的对映体，已成为新药研究和分析化学领域的重要课题。在药物对映体拆分分析研究中，常用的方法是气相色谱法和高效液相色谱法，这两种方法效率较高，但手性柱费用高、易污染，且手性衍生化常带进副产物；超临界流体色谱法处于发展阶段，各种参数对分离度的影响虽尚未完全清楚，但随着其理论和技术的日臻完善，这种方法在手性药物拆分中的应用将得到进一步发展；酶法和化学法在生产方面有较明显的优势，酶法操作简便且不易导致污染；而分子烙印技术有着良好的应用前景。     

超临界流体色谱技术在药物分析领域的应用研究进展

目的:为更好地促进超临界流体色谱(SFC)技术在药物分析工作中的应用提供参考。方法:以"超临界流体色谱""SFC""合相色谱""UPC""中药""Supercritical fluid chromatography""Ultra Performance convergence chromatography"等为关键词,组合查询在中国知网、万方数据库、维普数据库、Web of Science等数据库中收录的2012年1月-2017年6月发表的相关研究文献,进行归纳和总结。结果与结论:共检索到相关研究文献315篇,其中有效文献38篇。SFC技术实现分离主要原理是根据待测物在固定相和流动相两相中的分配系数不同,继而实现对待测物的先后洗脱。SFC技术在手性药物分析领域的应用主要涉及化学药手性成分拆分和中药手性成分拆分两个方面;在非手性药物分析领域的应用主要涉及天然产物分离及制备、代谢组学研究、维生素分离及测定和指纹图谱研究等方面。具有快速、高效、灵敏、环保等优点的SFC及其联用技术给药物成分的定性与定量分析提供了一条新的思路。     

离子对—超临界流体色谱在药物分析中的应用

针对超临界流体色谱分离强极性和离子型化合物时活脱时间长及色谱峰拖尾状况,发展了离子对－超临界流体色谱,该项技术是超临界流体色谱的一个有效补充手段,扩展了其分析对象的范围。本文就离子对－超临界流体色谱的装置、原理及其在药物分析方面的应用进行综述。     

超临界流体色谱仪在天然产物研究中的应用

超临界流体可以用作色谱的流动相,使混合物质在色谱柱上得到分离,这种分离方法被称为超临界流体色谱(supercritical fluid chromatography,SFC).作为色谱流动相的超临界流体,其作用与超临界流体萃取(supercritical fluid extraction,SFE)类似.超临界流体对物质的溶解能力比一般气体大的多,相当于有机溶剂,但比有机溶剂的扩散速度快、黏度低、表面张力小.超临界流体溶解能力的大小随其压力的变化而改变.由于超临界流体的黏度很低,SFC就可采用比高效液相色谱(HPLC)高的流速,因此具有分析/制备快的优点.     

超临界流体色谱在天然产物分析的研究进展

超临界流体色谱（Supercritical Fluid Chromatography,SFC）是一种绿色环保高效的分离技术,适于分离分析难挥发和热稳定性差的物质,流动相选择范围广且易得便宜,既可与气相色谱检测器联用也可与液相色谱检测器联用,弥补气相色谱和液相色谱的不足,对于复杂天然产物的分离纯化具备一定优势,对超临界流体色谱在天然产物分析的研究进行了综述。     

手性异构体拆分方法的研究进展

综述了近年来各种色谱分离方法在手性分离中的应用及进展。其中包括气相色谱法、液相色谱法、超临界色谱法、毛细管电泳和分子烙印法。     

Enantioselective chromatography in drug discovery

Molecular chirality is a fundamental consideration in drug discovery, one necessary to understand and describe biological targets as well as to design effective pharmaceutical agents. Enantioselective chromatography has played an increasing role not only as an analytical tool for chiral analyses, but also as a preparative technique to obtain pure enantiomers from racemates quickly from a wide diversity of chemical structures. Different enantioselective chromatography techniques are reviewed here, with particular emphasis on the most widespread high performance liquid chromatography (HPLC) and the rapidly emerging supercritical fluid chromatography (SFC) techniques. This review focuses on the dramatic advances in the chiral stationary phases (CSPs) that have made HPLC and SFC indispensable techniques for drug discovery today. In addition, screening strategies for rapid method development and considerations for laboratory-scale preparative separation are discussed and recent achievements are highlighted.     

多手性中心药物色谱拆分研究进展

多手性中心药物具有多个立体异构体,空间构型的差异导致异构体之间生物活性差异较大,多手性中心药物的手性分离分析仍然是一个巨大的挑战。关于单手性中心化合物手性分离分析的报道很多,而关于多手性中心药物的手性分离却非常少。本文总结了近年来关于多手性中心化合物色谱手性分离研究进展,主要包括HPLC、GC、毛细管电泳、超临界流体色谱及逆流色谱等在多手性药物分离分析中应用。     

Chiral separation by chromatographic and electromigration techniques. A review

This review gives a survey of different chiral separation principles and their use in high-performance liquid chromatography (HPLC), gas chromatography (GC), supercritical fluid chromatography (SFC), thin-layer chromatography (TLC), capillary electrophoresis (CE) and capillary electrochromatography (CEC) highlighting new developments and innovative techniques. The mechanisms of the different separation principles are briefly discussed and some selected applications are shown.     

环糊精及其衍生物在药物分离分析中的应用进展

近年来,环糊精及其衍生物在药物尤其是手性药物分离分析中的应用受到了广泛关注。本文通过查阅有关文献,对CD及其衍生物在高效液相色谱、气相色谱、毛细管电泳色谱、薄层色谱、超,临界流体色谱、高速逆流色谱以及膜分离等方法中的应用作了系统介绍,具有十分重要的参考价值。     

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%.     

超临界流体色谱拆分齐留通对映体

目的研究超临界流体色谱对齐留通对映体的分离效果。方法考察确定5种手性柱中分离效果最佳的柱子,在该柱上考察改性剂的种类、浓度、温度及背压对分离度的影响。结果采用Chiralpak AD-H柱、改性剂为异丙醇,异丙醇在流动相中比例为18%、背压为140 bar、温度为303 K时,齐留通对映体达到最佳分离,分离度为11.5,出峰时间分别为4.59、7.35min。结论所用超临界流体色谱的方法简单、快捷、经济有效,适用于齐留通对映体的分离。     

手性药物分析方法研究进展

综述了近10年来手性药物分离检测方法的发展,包括高效液相色谱法、气相色谱法、毛细管电泳法,以及超临界流体色谱法等,旨在为该领域的进一步发展提供参考。     

Enantioseparation of chiral vasodilator drug isoxsuprine in high-performance liquid chromatography and capillary electrophoresis.

Two independent methods using high-performance liquid chromatography (HPLC) on polysaccharide type chiral stationary phase (CSP) and capillary electrophoresis (CE) with native and derivatised cyclodextrins (CD) have been proposed for the enantioseparation of chiral vasodilator drug isoxsuprine (ISP). The methods have been compared from the viewpoint of separation characteristics (efficiency, sensitivity, analysis time, costs, etc.).     

A feasibility study on direct assay of an aqueous formulation by chiral supercritical fluid chromatography (SFC)

Supercritical fluid chromatography (SFC) has gained considerable importance in the area of Separation Science in pharmaceutical analysis over the past few years. The synthesis of chiral compounds is of particular significance in the pursuit of new drug entities. SFC is rapidly replacing high performance liquid chromatography (HPLC) in many pharmaceutical and biotechnological companies as the standard screening and method development tool for chiral compounds. Analysis of pharmaceutical formulations of research compounds is an area where SFC is recently being explored as a possible alternate or complementary technique to HPLC in limited scope. A feasibility study was carried out to perform direct assay of a chiral drug compound AZM in 100% aqueous formulations by SFC. The results indicated that this approach has the potential to significantly reduce the typical sample processing time prior to analysis. The method was reproducible, linear over a wide dynamic range, and sensitive enough to detect the minor enantiomeric impurity in the chiral drug compound investigated here. Further application will be pursued for other research compounds in the future to illustrate the broader applicability of this approach.