摘要
目前使用的绝大多数药物为手性化合物,它们具有相似的物理和化学性质,但药理活性不同,且常以外消旋混合物的形式存在,因此对手性化合物的分离在生物、环境、食品和医药等领域一直备受关注。与广泛使用的液相色谱-质谱(LC-MS)相比,毛细管电泳-质谱(CE-MS)作为一种新型分离分析技术,具有分离效率高、样品和试剂消耗量低、选择性高和分离模式多样化等诸多优势,已经发展成为手性分析领域中有广阔应用前景的分析方法之一。CE-MS结合了CE的高分离效率和低样品消耗以及MS的高灵敏度和强结构解析能力,在蛋白质组学和代谢组学等领域发挥了重要作用。CE杰出的手性拆分能力与MS优势的结合,亦使CE-MS成为实现手性化合物高效分离分析的完美组合。在过去的十几年里,基于不同CE-MS分离模式的高性能手性分析体系层出不穷,如电动色谱-质谱(EKC-MS)、胶束电动色谱-质谱(MEKC-MS)和毛细管电色谱-质谱(CEC-MS)等,并成功应用于医药、生物、食品和环境科学等领域的手性化合物分析。该文主要综述了2011~2021年,CE-MS在手性化合物分析领域的技术、手性选择剂(如改性环糊精和聚合物表面活性剂等)的使用以及在医药等领域应用方面的研究进展,并讨论了不同手性分析模式的局限性,为未来的CE-MS手性分离分析技术发展及应用提供借鉴。
Most drugs used to treat diseases are chiral compounds.Drug enantiomers possess similar physical and chemical properties but may feature distinct pharmacological activities.Drug enantiomers may also exhibit different or even opposite functionalities for metabolism,in terms of the metabolic rate and toxicity in the body.Therefore,it is imperative to analyze,separate,and purify the enantiomers of drugs.The separation of chiral compounds is essential for drug research and development.It is also of significance in various fields including biological environments,food,and medicine.Various highly selective and sensitive methods have been developed for the quantitative and qualitative analyses of chiral compounds.A typically employed technique is high performance liquid chromatography-mass spectrometry(HPLC-MS).While HPLC-MS offers high sensitivity and reproducibility,it requires expensive chiral columns and MS-compatible mobile phases for the chromatographic column.Further,the column efficiency and resolution capacity in chiral chromatography packing require improvement.Recent progress has shown that capillary electrophoresis-mass spectrometry(CE-MS)has broad applications in chiral analysis.As a well-established analytical technique,CE-MS combines the highly efficient separation technique of CE with the highly sensitive detection technique of MS.Thus,it offers many essential advantages for analysis.For example,CE-MS has a high separation efficiency and requires very low amounts of samples and reagents.It can also achieve sensitive and selective determination,and the obtained diversified separation modes can be used for different samples.Therefore,CE-MS has proved to be important in analytical chemistry,especially in proteomics and metabolomics.CE can also exhibit excellent performance in chiral separation.Hence,combined with the sensitive detection technique of MS,CE-MS would be ideal for chiral analysis.Chiral CE-MS can provide a wide range of qualitative information on samples simultaneously in a single run,including the migration time,relative molecular mass,and ionic fragments.It addresses the challenges associated with identifying unknown chiral compounds in actual samples(including chiral compounds without UV absorption groups or fluorescence groups).The high-throughput analysis of multiple groups of chiral enantiomers can be achieved while mitigating the matrix effect of biological samples.In the last ten years,high performance chiral analysis strategies based on different CE-MS modes have been developed.These include electrokinetic chromatography-mass spectrometry(EKC-MS),micellar electrokinetic chromatography-mass spectrometry(MEKC-MS),and capillary electrochromatography-mass spectrometry(CEC-MS).CE-MS has been successfully applied in chiral analysis in various fields such as medicine,biology,food,and environmental science.CE-MS is promising in the chiral analysis of drugs,especially for drug development and drug quality control,as well as pharmacokinetics and pharmacodynamics research.Recent studies have focused on the development of MS-friendly and highly selective chiral analytical methods,which will broaden the application of CE-MS.In CEC-MS chiral analysis,more attention has been paid to developing novel capillary chiral stationary phases for monolithic or packed columns.Because of the diversity of chiral selectors for EKC-MS and MEKC-MS,the chiral analysis of drugs using these techniques has attracted intense research interest.Moreover,functional nanoparticles have been employed to increase the surface area of the CEC columns for enhancing the efficiency of chiral analysis.The chiral separation and analysis of miniaturized microchip equipment via CE-MS has also been explored,but remains to be widely used in practical applications.The purpose of this review is to provide insights that would aid in broadening the applications of CE-MS to chiral analysis.In this review,we primarily summarize research progress on the application of CE-MS to chiral analysis,based on the literature published during the years 2011-2021.Chiral selectors(e.g.,modified cyclodextrin and polymer surfactants)and their reported applications in CE-MS are presented.The determination results for drug enantiomers using different CE-MS modes are compared.The application of CE-MS in other research fields is also presented,along with the advantages and limitations of different CE-MS methods.
作者
迟忠美
杨丽
CHI Zhongmei;YANG Li(College of Chemistry and Materials Engineering, Bohai University, Jinzhou 121013, China;Faculty of Chemistry, Northeast Normal University, Changchun 130024, China)
出处
《色谱》
CAS
CSCD
北大核心
2022年第6期509-519,共11页
Chinese Journal of Chromatography
基金
国家自然科学基金面上项目(22074014)
渤海大学博士启动基金(0521bs018).
关键词
毛细管电泳
质谱
手性化合物
综述
capillary electrophoresis(CE)
mass spectrometry(MS)
chiral compounds
review