Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, Madrid, Spain.
Instituto de Investigación Química, "Andrés M. del Río" (IQAR), Universidad de Alcalá, Ctra. Madrid-Barcelona Km. 33.600, Alcalá de Henares, Madrid, Spain.
Crit Rev Anal Chem. 2020;50(6):554-584. doi: 10.1080/10408347.2019.1670043. Epub 2019 Oct 1.
Chirality is a relevant issue in the pharmaceutical field due to the different biological activity that enantiomers of a chiral drug can show. In fact, the desired biological or pharmaceutical activity might be present in only one of the enantiomers, while the other enantiomer(s) may have different biological activity, be inactive or even toxic. This has motivated in recent years the development of drugs marketed as pure enantiomers to avoid exposing the organism to the action of enantiomers that may not be active or even harmful to health. Thus, it is of high interest to develop enantioselective analytical methodologies to control the presence of enantiomeric impurities and to understand the enantioselective metabolism of chiral drugs. This review gives an overview about the analytical strategies developed by electrokinetic chromatography (EKC) from 2010 to June 2019 for the enantiomeric determination of drugs in both pharmaceutical formulations and biological samples. The types of chiral selectors used, the migration order of enantiomers, their resolution, the detection technique employed and the sensitivity achieved are revised and compared. Also, applications to assess the enantiomeric purity control of pharmaceutical formulations and to determine chiral drugs in biological samples to study their metabolism are included. Advantages and limitations of the chiral methods developed by EKC are also discussed.
手性在制药领域是一个相关的问题，因为手性药物的对映异构体可能表现出不同的生物活性。事实上，只有一种对映异构体可能具有所需的生物或药物活性，而其他对映异构体可能具有不同的生物活性、无活性甚至有毒。这促使近年来开发了作为纯对映异构体上市的药物，以避免使生物体暴露于可能无活性甚至对健康有害的对映异构体的作用下。因此，开发对映体选择性分析方法来控制对映异构体杂质的存在以及了解手性药物的对映体代谢具有重要意义。本综述概述了 2010 年至 2019 年 6 月期间，电泳色谱（EKC）用于药物在药物制剂和生物样品中对映体测定的分析策略。综述了所使用的手性选择器的类型、对映体的迁移顺序、它们的分辨率、所采用的检测技术和获得的灵敏度，并进行了比较。还包括了用于评估药物制剂对映体纯度控制和在生物样品中测定手性药物以研究其代谢的应用。还讨论了 EKC 开发的手性方法的优缺点。
