Analytical and Preparative Scale Separation of Enantiomers of Chiral Drugs by Chromatography and Related Methods

Abstract

While the amino acids, enzymes and hormones are chiral, chirality plays significant role in the life of plants, animals, as well as the human being. Chirality of molecules is important in various industries, such as pharmaceutical, agricultural, food, electronics, etc. Chiral drugs may have different bioavailability, distribution, biotransformation and excretion, as well as quantitatively and/or qualitatively different pharmacological or toxic properties. Enantiomerically pure chiral drugs have been increasingly developed for the pharmaceutical market due to their superiority from the viewpoints of potency and safety. This is supported by the development of new methods for enantioselective production of the chiral compounds, as well as by the capability of the enantioselective analytical methods to allow a detection and quantification of minor enantiomeric impurity in the presence of another enantiomer in a large excess. The aim of the present review is to provide a short summary of the basic principles of chiral separations on an analytical and preparative scale. In addition, some selected applications for analytical techniques, such as gas chromatography, supercritical fluid chromatography, high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography for the separation of enantiomers of chiral pharmaceuticals published in the last two years are also discussed.

Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

“…In these stages, the costs and scale-up potential of the method become a very important issue to be considered [17]. There are prevailing resolution techniques and strategies to obtain the enantiomers in this scale including crystallization [29,30], simulated moving bed (SMB) [31], and liquid chromatography (LC) [14,22,27]. Leek H. et al [32] recently reported a strategy for large-scale isolation of enantiomers in drug discovery, affording different options that involved different chromatographic techniques together with crystallization.…”

“…In response to the exponential research in Medicinal Chemistry concerning the invention, discovery, design, identification and preparation of new biologically active compounds in enantiomerically pure form, aligned to the stricter requirements from regulatory authorities to patent new chiral drug [11], the development of methods for enantioselective production of chiral compounds as well as evaluation of their enantiomeric purity, proved to be essential. Accordingly, different enantioselective synthetic methodologies were developed [12,13] in addition to diverse analytical and preparative techniques [14,15]. Nevertheless, pure enantiomers can be achieved using several methods as illustrated in Figure 1.…”

Preparation and evaluation of partially‐substituted 3‐chloro‐4‐methylphenylcarbamate‐β‐cyclodextrin bonded silica particles as chiral stationary phase for multi‐mode HPLC

“…It is well known that enantiomers of a chiral drug compound can produce different potencies, toxicity, and behavior in biological systems . Development of new chiral stationary phases (CSPs) possessing high enantioselectivity for efficient chiral separations of chiral drug compounds is still an active and important field in HPLC . Due to the special spatial structure and properties of native β‐cyclodextrin (β‐CD) and its derivatives, the β‐CD‐based CSPs play important roles in the separation of chiral drugs .…”

Characterization of Amino Acid Based Molecular Micelles with Molecular Modeling

“…Many techniques such as gas and liquid chromatography [1]- [9] and capillary electrophoresis (CE) [10]- [19] have been developed to separate the enantiomers of chiral compounds. These separations are used to analyze the results of chiral drug syntheses and to confirm the enantiomeric purity of commercial drug formulations.…”