Chiral analysis

Indirect enantiomer separation

3-Point interaction model

Structure of native cyclodextrins

Sketch of cone shape of cyclodextrin

Chiral analysis is a critical aspect of chemistry and pharmacology that involves the study and determination of the chirality or handedness of a molecule. Chirality is a geometric property of some molecules and ions; a chiral molecule/ion is non-superimposable on its mirror image. The presence of chirality is significant because the two mirror images, known as enantiomers, can have vastly different properties, especially in their biological activities. This makes chiral analysis essential in the synthesis, characterization, and quality control of pharmaceuticals, agrochemicals, and other chiral substances.

Overview

Chiral analysis aims to identify the enantiomeric composition of a sample, which involves determining the relative amounts of enantiomers present. This is crucial because, in many cases, only one enantiomer is therapeutically active, or one may be more active than the other. In some instances, the enantiomers of a drug can have entirely different pharmacological effects. For example, one enantiomer may be beneficial, while the other could be harmful or less effective. Therefore, chiral analysis is not only important for understanding the pharmacodynamics and pharmacokinetics of drugs but also for ensuring the safety and efficacy of chiral drugs.

Techniques for Chiral Analysis

Several analytical techniques are employed for chiral analysis, each with its advantages and limitations. The choice of method depends on the specific requirements of the analysis, such as sensitivity, selectivity, and the nature of the sample.

Chromatography

Chromatography is one of the most widely used techniques for chiral analysis. Chiral chromatography involves the separation of enantiomers using a chiral stationary phase (CSP). The most common forms of chiral chromatography are:

• High-performance liquid chromatography (HPLC) with chiral stationary phases
• Gas chromatography (GC) with chiral stationary phases
• Supercritical fluid chromatography (SFC) with chiral stationary phases

These methods rely on the differential interactions between the enantiomers and the CSP to achieve separation.

Capillary Electrophoresis

Capillary electrophoresis (CE) is another technique used for chiral analysis. It separates ions based on their charge-to-size ratio in a capillary filled with an electrolyte. Chiral CE can be achieved by adding chiral selectors to the electrolyte, which form transient diastereomeric complexes with the analytes, leading to their separation.

Spectroscopy

Certain spectroscopic methods can also be used for chiral analysis, including:

• Circular dichroism (CD) spectroscopy, which measures the difference in the absorption of left-handed and right-handed circularly polarized light by chiral molecules.
• Nuclear magnetic resonance (NMR) spectroscopy, where chiral solvating agents or chiral derivatizing agents are used to create diastereomeric complexes, which have different NMR signals.

Applications

Chiral analysis is indispensable in the pharmaceutical industry for the development and quality control of chiral drugs. It is also crucial in environmental chemistry for the analysis of chiral pollutants, in food chemistry for the analysis of natural products, and in forensic science for the analysis of chiral compounds in biological samples.

Regulatory Aspects

Regulatory agencies, such as the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) in Europe, have issued guidelines for the development and approval of chiral drugs. These guidelines often require detailed chiral analysis to ensure the safety and efficacy of these drugs.