超临界流体色谱手性分析,第1部分:理论背景

G. Roskam, Bas van de Velde, Andrea F. G. Gargano, Isabelle Kohler
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引用次数: 3

摘要

外消旋物质对映体的定量在药物化合物的开发和调控中具有重要意义。活性成分通常是手性的;通常,只有一种立体异构体具有所需的药代动力学和/或药效学性质。因此,在药物发现和开发过程中,必须对手性药物的立体异构体分布进行表征和评价。此外,各种手性药物呈现出立体选择性代谢,强调需要适当的分析策略来进行代谢物的立体选择性分析,例如在临床和环境研究中。由于其易于使用,鲁棒性和可转移性,手性液相色谱(LC)是药物分析中最常用的方法。与LC相比,超临界流体色谱(SFC)允许更高的线性流速,同时保持较高的色谱效率,通常可以减少分析时间。此外,SFC提供增强或互补的手性选择性,避免或减少有毒溶剂,如在正相LC中使用的溶剂。本文第一部分综述了手性SFC的理论优势、技术发展和常用实践。随后将讨论在制药、临床、法医和环境分析方面的最新应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Supercritical Fluid Chromatography for Chiral Analysis, Part 1: Theoretical Background
The quantification of the enantiomers of racemic substances is of great importance in the development and regulation of pharmaceutical compounds. Active ingredients are often chiral; typically, only one of the stereoisomers has the desired pharmacokinetic and/or pharmacodynamic properties. Therefore, the stereoisomer distribution of chiral drug products must be characterized and evaluated during the drug discovery and development pipeline. Moreover, various chiral drugs present a stereoselective metabolism, highlighting the need for appropriate analytical strategies for the stereoselective analysis of metabolites, for example, in clinical and environmental studies. Due to its ease of use, robustness, and transferability, chiral liquid chromatography (LC) is the most common approach used in pharmaceutical analysis. Compared with LC, supercritical fluid chromatography (SFC) allows higher linear flow velocities while maintaining high chromatographic efficiency, often enabling the reduction of analysis time. In addition, SFC provides enhanced or complementary chiral selectivity and avoids or reduces toxic solvents, such as those used in normal-phase LC. In the first part of this review article the theoretical advantages, technological developments, and common practices in chiral SFC are discussed. This will be followed by a contribution discussing recent applications in pharmaceutical, clinical, forensic, and environmental analysis.
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