毛细管电泳在手性分离中的应用及进展

本文评述了近年来毛细管电泳在手性分离中的应用及进展，介绍了毛细管电泳分离手性对映射的数学模型、五种不同的分离模式及机理、七种常用的手性选择性类型及其在药学、环境和生命科学中的应用、研究中需优化的操作参数及其发展方向。     

Recent advances in peptide chiral selectors for electrophoresis and liquid chromatography

The application of peptides in chiral separations using techniques such as capillary electrophoresis (CE), electrokinetic capillary chromatography (EKC) and liquid chromatography is the focus of this review. Methods for finding peptide selectors using combinatorial library approaches are discussed, as well as recent advances in the use of peptides as general chiral selectors for electrophoresis and liquid chromatography. One example shows the effectiveness of polymeric dipeptide surfactants as general chiral selectors for electrophoresis. Another example shows the versatility of oligoproline chiral stationary phases, exhibiting resolution for a number of racemic analytes comparable to other well-established chiral stationary phases.     

毛细管电泳手性分离进展*

评述了近年来毛细管电泳手性分离的进展。以各种手性选择剂的发展为线索介绍了毛细管电泳手性分离理论、方法及应用。简要说明了分离中应注意的一些关键问题。     

手性环境污染物的毛细管电泳分离技术进展

围绕毛细管电泳(CE)技术近10年来在分离手性环境污染物方面的应用进行了介绍。对CE手性分离技术的特点做了简要概括,归纳了目前用于CE手性分离的手性选择剂。对CE技术在分离除草剂、杀虫剂、杀真菌剂以及多氯联苯(PCBs)等手性环境污染物方面的应用进行了综述,并对CE在手性环境污染物分离中的应用提出新的研究方向。     

Recent advances in chiral separation principles in capillary electrophoresis and capillary electrochromatography

This review summarizes recent developments in chiral separation in capillary zone electrophoresis (CZE), electrokinetic chromatography (EKC), and capillary electrochromatography (CEC) covering literature published since the year 2000. New chiral selectors and innovative approaches for CE and CEC are introduced. Recent progress in column technology for CEC is highlighted and the development of new chiral stationary phases is discussed. This review is not dedicated to list applications but will focus on new developments.     

毛细管电泳新型手性分离体系研究进展

在现代分离科学中,手性化合物的分离分析一直是研究的重点和难点。相比于高效液相色谱（HPLC）、气相色谱（GC）等传统色谱分析方法,毛细管电泳（CE）技术凭借其高效率、低消耗、分离模式多样化等诸多优势,已经发展成为手性分离研究领域最有应用前景的分析方法之一。近年来,研究人员在CE手性分析方法的构建过程中,基于毛细管电动色谱（EKC）、配体交换毛细管电泳（LECE）、毛细管电色谱（CEC）等各种基础电泳模式,不断地对传统手性分离体系进行优化和改造,构建出了许多高性能的新型手性CE分离体系。如利用各类功能化离子液体以"手性离子液体协同拆分""手性离子液体配体交换""离子液体手性选择剂"等模式设计出多种基于离子液体的CE手性分离体系;利用纳米材料独特的尺寸效应、多样性、可设计性等特点,直接或与传统手性选择剂有机结合构建CE手性分离体系。此外,金属有机骨架材料修饰、低共熔溶剂修饰、非连续分段式部分填充等各式新颖的CE手性分离体系也都被研究人员成功开发,并表现出较大的发展潜力。该综述将对近年来（尤其是2015~2019年）此类新型CE手性分离体系的发展状况进行梳理,并结合相应的手性识别机理研究和手性CE方法实际应用情况,对该领域存在的问题及发展前景进行分析和展望。     

Recent advances of capillary electrophoresis in pharmaceutical analysis

This review covers recent advances of capillary electrophoresis (CE) in pharmaceutical analysis. The principle, instrumentation, and conventional modes of CE are briefly discussed. Advances in the different CE techniques (non-aqueous CE, microemulsion electrokinetic chromatography, capillary isotachophoresis, capillary electrochromatography, and immunoaffinity CE), detection techniques (mass spectrometry, light-emitting diode, fluorescence, chemiluminescence, and contactless conductivity), on-line sample pretreatment (flow injection) and chiral separation are described. Applications of CE to assay of active pharmaceutical ingredients (APIs), drug impurity testing, chiral drug separation, and determination of APIs in biological fluids published from 2008 to 2009 are tabulated.     

毛细管电泳在手性化合物分离分析中的研究进展

手性化合物的对映异构体往往表现出不同的生理活性,因此建立手性化合物的有效分离分析方法具有重要意义。毛细管电泳（CE）是一种分离效率高、分析速度快、样品用量少、分离模式灵活多样的分离分析方法,在手性化合物的分离和检测领域应用广泛。该文主要综述了2017~2019年CE在手性分离分析方面的最新进展,并对其未来的发展趋势进行了展望。     

Sensitive chiral analysis by CE: an update

A general view of the different strategies used in the last years to enhance the detection sensitivity in chiral analysis by CE is provided in this article. With this purpose and in order to update the previous review by García-Ruiz et al., the articles appeared on this subject from January 2005 to March 2007 are considered. Three were the main strategies employed to increase the detection sensitivity in chiral analysis by CE: (i) the use of off-line sample treatment techniques, (ii) the employment of in-capillary preconcentration techniques based on electrophoretic principles, and (iii) the use of alternative detection systems to the widely employed on-column UV-Vis absorption detection. Combinations of two or three of the above-mentioned strategies gave rise to adequate concentration detection limits up to 10(-10) M enabling enantiomer analysis in a variety of real samples including complex biological matrices.     

The role of cyclodextrins in chiral capillary electrophoresis

The members of the enantiomeric pairs frequently show rather different biological effects, so their chiral selective synthesis, pharmacological studies and analysis are necessary. CE has unique advantages in chiral analysis. The most frequently used chiral selectors are CDs in this field. This paper gives a short view on the advantages on CE in direct chiral separations, emphasizing the role of CDs. The reason for the broad selectivity spectra of CDs is discussed in detail. The physical background of chiral selective separations is briefly shown in CE. Their interaction mechanisms are shortly defined. The general trend of their use is statistically evaluated. Most frequently used CDs and CD derivatives are characterized. Advantages of ionizable CDs and single-isomer derivatives are shown. The general trend of their use is established.     

Generic capillary electrophoresis conditions for chiral assay in early pharmaceutical development

Generic capillary electrophoresis (CE) conditions have been implemented for chiral separations in early pharmaceutical development. The chiral CE separations of several pharmaceutical samples at different stages of development, i.e., discovery, process chemistry, and investigative new drug application, have been obtained using sulfated beta-cyclodextrin (CD). Several sulfated beta-CDs have been screened to select an appropriate enantioselective agent. The use of a generic CE method allows for a convenient and rapid chiral recognition of different weak bases, with minimal or no method development. CE using sulfated beta-CD for the chiral separation of N-benzoyl methyl piperazine has been validated for linearity, precision, accuracy, limits of detection and quantitation (LOD, LOQ). Although less sensitive than a specific liquid chromatography method using a Chiralpak AD column, the overall performance of the chiral CE method was found comparable. Validation data demonstrate that a LOD of 0.1%, sufficient to fulfill regulatory requirements, is achievable by chiral CE.     

毛细管电泳用于药物分析的研究进展

药物分析是毛细管电泳（CE）的重要应用领域,所有CE分离模式与检测方法都在各种药物及其不同形式样品的分离分析中显示出特色和应用能力。该文从药品分析领域中的小分子药物（包括手性药物）及其有关物质、中药与天然产物、体内药物分析、生物制品药物分析等几个方面,综述了近几年CE在这些传统药物分析领域应用的研究进展。限于篇幅,未包括现代药物分析研究比较活跃的理化常数测定、亲和毛细管电泳与结合常数研究（药物与受体间的相互作用等）、临床生物标志物分析、代谢组学和微流控芯片CE分析等方面的内容。根据目前传统药物分析领域的发展,该文关注到近期CE在顺应药物分析的法规需求、电容耦合非接触电导检测（CE-C⁴ D）、改进检测灵敏度与精密度、CE-十二烷基硫酸钠（SDS）毛细管电泳、全柱成像毛细管等电聚焦（icIEF）、抗体分析等方面的新进展。该文结合文献,讨论了目前传统药物分析领域的需求,以及CE在其中的地位、挑战和机遇。对目前CE主要作为互补分析方法在化学药和中药分析中的应用研究提出了一些针对性的建议,期待CE在生物制品分析中的特色和能力得到进一步的发挥,同时提出CE-MS和对CE分析重复性改进等新进展可能对未来CE应用领域的大幅度扩展。该综述主要涉及近3年（2017年1月到2020年2月）及部分2016年的相关文献。     

Recent progress in pharmacokinetic applications of capillary electrophoresis

This review is a continuation of the previous reviews (Electrophoresis 1999, 20, 3259-3268; Electrophoresis 2001, 22, 4244-4248) to update the recent publications from 2001 to 2003 on pharmacokinetic studies using capillary electrophoresis (CE). During this period of time, CE remains as a unique analytical method for some studies, which would otherwise be limited by many factors, such as the sample volume, detection sensitivity, or separation power. It is particularly noticeable that the separation of chiral drugs in biological sample and the use of solid-phase extraction (SPE) as a simple and convenient means of sample preparation appear to become popular for CE-based assays. The use of CE for assessing complete pharmacokinetic information, however, did not show a significant growth during this period of time. In order to provide a broad range of view on how biological samples are analyzed by CE, this review will cover publications during the past two years on the use of CE for the analysis of drugs in biological fluids for general pharmacokinetic applications including drug monitoring and bioavailability studies.     

Recent advances in CE-MS: Synergy of wet chemistry and instrumentation innovations

CE with MS detection is a hyphenated technique which greatly improves the ability of CE to deal with real samples, especially with those coming from biology and medicine, where the target analytes are present as trace amounts in very complex matrices. CE-MS is now almost a routine technique performed on commercially available instruments. It faces currently a tremendous development of the technique itself as well as of its wide application area. Great interest in CE-MS is reflected in the scientific literature by many original research articles and also by numerous reviews. The review presented here has a general scope and belongs to a series of regularly published reviews on the topic. It covers the literature from the last 2 years, since January 2008 till June 2010. It brings a critical selection of related literature sorted into groups reflecting the main topics of actual scientific interest: (i) innovations in CE-ESI-MS, (ii) use of alternative interfaces, and (iii) ways to enhance sensitivity. Special attention is paid to novel electrolyte systems amenable to CE-MS including nonvolatile BGEs, to advanced CE separation principles such as MEKC, MEEKC, chiral CE, and to the use of preconcentration techniques.     

Utility of ionic liquids in analytical separations

Ionic liquids (ILs), as separation media, have made significant contributions in the past decades in advancing research in gas chromatography (GC), liquid chromatography (LC), and capillary electrophoresis (CE). This review, covering reports published from the mid 1980s to early 2007, shows how ILs have been used so far in separation science, originally primarily as GC stationary phases and later as mobile phase additives (both millimolar and major percent levels) for LC and CE. Representative GC and LC chromatograms as well as CE electropherograms are shown. In addition, the very recent findings on the development of ionic liquids with surfactant properties and its applications for chiral and achiral analysis are discussed.     

The Use of Dual Cyclodextrin Chiral Selector Systems in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: An Overview

Cyclodextrin (CD) derivatives are the most efficient and frequently used chiral selectors (CSs) in capillary electrophoresis (CE). There are situations when the use of a single CD as CS is not enough to obtain efficient chiral discrimination of the enantiomers; in these cases, sometimes this problem can be resolved using a dual CD system. The use of dual CD systems can often dramatically enhance enantioseparation selectivity and can be applied for the separation of many analytes of pharmaceutical interest for which enantioseparation by CE with another CS systems can be problematic. Usually in a dual CD system an anionic CD is used together with a neutral one, but there are situations when the use of a cationic CD with a neutral one or the use of two neutral CDs or even two ionized CDs can be an efficient solution. In the current review we present general aspects of the use of dual CD systems in the analysis of pharmaceutical substances. Several examples of applications of the use of dual CD systems in the analysis of pharmaceuticals are selected and discussed. Theoretical aspects regarding the separation of enantiomers through simultaneous interaction with the two CSs are also explained. Finally, advantages, disadvantages, potential and new direction in this chiral analysis field are highlighted.     

Overview of the status and applications of capillary electrophoresis to the analysis of small molecules

The status of capillary electrophoresis (CE) in the analysis of small molecules is reviewed and summarised with the illustrative use of recent literature references. Examples are cited in this review which demonstrate that CE is now a recognised and established technique in many industries, law courts and government regulatory agencies. Each of the principal areas of CE application in small molecule analysis are covered in sections which highlight the recent developments and possibilities within that area. Application areas include the analysis of pharmaceuticals, agrochemicals, chiral separations, and forensics is covered. This is an update to a previous review article [J. Chromatogr. A 856 (1999) 443] and covers papers published between 1999 and 2002. Technical developments and improvements, such as the advent of capillary array instrumentation for increased sample throughput, and improved detection options are described. Overall it is concluded that CE has become a recognised and established technique in many areas and is still within a period of development of both instrumentation and application which will continue to expand usage.     

Chiral separations by capillary electromigration techniques in nonaqueous media. I. Enantioselective nonaqueous capillary electrophoresis

Enantiomer separations by CE employing nonaqueous conditions are reviewed. The general focus of this article is directed towards solvent effects on chiral recognition and the separation mechanism. After a general discussion of solvent effects on the individual processes involved in CE enantiomer separation, specifics for various selector classes are discussed together with a few applications of enantioselective nonaqueous CE.     

Enantiomer separation of drugs by capillary electrophoresis using proteins as chiral selectors

The separation of drug enantiomers using proteins as the chiral selectors in capillary electrophoresis (CE) is considered in this review. The proteins used include albumins such as bovine serum albumin, human serum albumin and serum albumins from other species, glycoproteins such as alpha1-acid glycoprotein, crude ovomucoid, ovoglycoprotein, avidin and riboflavin binding protein, enzymes such as fungal cellulase, cellobiohydrolase I, pepsin and lysozyme and other proteins such as casein, human serum transferrin and ovotransferrin. Protein-based CE is carried out in two modes: in one proteins are immobilized or adsorbed within the capillary, or protein-immobilized silica gels are packed into the capillary (affinity capillary electrochromatography mode), and in the other proteins are dissolved in the running buffer (affinity CE mode). Furthermore, the advantages and limitations of the two modes and the factors affecting the chiral separations of various drugs by protein-based CE are discussed.