Chiroptical Spectroscopy in Drug Analysis

Author:

Rodger Alison

Abstract

Abstract Many pharmaceutical compounds contain one or more centers of dissymmetry, thus presenting a unique series of regulatory and compendial requirements. The regulatory authorities are well acquainted with the fact that one given enantiomer or diastereomer of a drug entity may possess more efficacy (or fewer side effects) than its mirror image. Consequently, unless a compelling argument exists for the marketing of a 50:50 racemic mixture, it is more appropriate to develop enantiomerically pure therapeutic agents. Although often characterized using chiral chromatography, these molecules can be effectively studied using the various techniques of chiroptical spectroscopy. Techniques that have been found to be very useful for such work include polarimetry (i.e. circular birefringence), optical rotatory dispersion ( ORD ), and circular dichroism ( CD ). At present, polarimetry remains the main technique used by regulatory authorities to establish enantiomeric identity and purity; however, more sophisticated chiroptical techniques are increasingly being used especially for biopharmaceuticals. In this article, the principles underlying each chiroptical effect are briefly outlined, and the application to problems of pharmaceutical interest is illustrated through the inclusion of appropriate examples.

Publisher

Wiley

Reference51 articles.

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