Chiral analysis of pharmaceuticals

That the resolution of the enantiomers of chiral drugs should be considered as a topic in its own right in a treatise on pharmaceutical analysis should come as no surprise. The importance of chirality in many fields of natural and applied science is well established [1]. In pharmaceutical analysis, this topic which commands its own nomenclature (Table 3.1) is especially important, as is apparent from the proportion of drugs on the market that are chiral (Table 3.2). 

Chiral molecules Molecules whose mirror images are not superimposable upon each other. 

Stereoisomers Compounds, die molecules of which have die same atoms connected in order 

Enantiomers One of a pair of molecular species diat are mirror images of each other and not 

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Erny, G. L., and Cifuentes, A. (2006). Liquid separation techniques coupled with mass spectrometry for chiral analysis of pharmaceuticals compounds and their metabolites in biological fluids. ]. Pharm. Biomed. Anal. 40, 509—515. 

Just as modem liquid chromatography (LC) is the dominant separative technique in the analysis of pharmaceuticals, so, in the evolution of methodologies for the chiral analysis of pharmaceuticals, LC has emerged as the pre-eminent technique. As already intimated, discrimination between enantiomers requires the presence of a chiral selector. In the determination of enantiomers by LC... 

LC is undoubtedly the most important technique in the chiral analysis of pharmaceuticals. However, that is not to say that chiral LC of pharmaceuticals is synonomous with chiral analysis of pharmaceuticals. The chiral selectors utilised in LC may be usefully deployed in a range of other analytical techniques. Despite this, chiral LC is more dominant now than it ever was. The early commercial developments in chiral analysis were in LC. The application of similar selector systems was demonstrated in other techniques but now with the notable exception of chiral capillary electrophoresis (CE) there is a strong reliance again on LC. 

One thing that is certain with the developments in chiral selectors and their applications that have been described is that they will continue, whether it be by gradual evolutionary fine-tuning in an already mature area or by some yet unforeseen major advances. What is of more importance is how these developments currently shape up with respect to the applications presented by the chiral analysis of pharmaceuticals. 

Maftouh, M., Granier-Loyaux, C., Chavana, E., Marini, J., Pradines, A., Vander Heyden, Y., Picard, C. Screening approach for chiral separation of pharmaceuticals Part in. Supercritical fluid chromatography for analysis and purification in drug discovery. J. Chromatogr. A 2005, 1088, 67-81. 

Enantioselectivity was introduced especially for use in analysis of pharmaceuticals, where it was found that some pharmaceutical products have a chiral center and only one of the enantiomers exhibits the required pharmacological and pharmacokinetic behavior. The term was introduced first in relation to separation techniques,278 281 and later sensor technology.282... 

SFC has been undergoing a renaissance in its use in modem analytical laboratories over the last decade, particularly in chiral and achiral analysis of pharmaceutical compounds. Many of the problems associated with implementing SFC have come from the teclmical and operational difficulties in earlier instruments [134, 135]. New developments in SFC include improved backpressure-regulation, more consistent SFC flow rates, more reliable sample injection systems and improved flow cell designs [136,137]. 

One of the most important and challenging areas in the analysis of pharmaceuticals is the determination of chiral purity. It is therefore highly appropriate that a chapter is devoted to this area. The importance of chiral analysis is described, together with the development of techniques across the separation sciences and beyond. 

This chapter will look at the use of CE for pharmaceutical analysis and will include descriptions of the various modes of CE and their suitability for quantitative and qualitative analysis of pharmaceutical compounds. Practical applications of CE for the analysis of pharmaceuticals will be covered, these applications include drug assay, impurity determination, physicochemical measurements, chiral separations, and the analysis of small molecules. A section covering the approach to CE method development for pharmaeeutical analysis will include guidelines to selecting the best mode of CE for an intended separation. Extensive data will be provided on successful pharmaceutical separations with references to extra source material for the interested reader. This chapter will provide a comprehensive and up to date view of the role and importance of CE for the analysis of pharmaceuticals and will provide the reader with practical information and real data that will help them to decide if CE is suitable for an intended separation. 

Chiral CE using mass spectrometric detection has also been utilized for detailed qualitative analysis of pharmaceuticals, a review by Shamsi [115] covers the various modes of CE-MS including the use of neutral CDs for FSCE-MS and MEKC-MS. 

Self-assembled monolayer and layer-by-layer approaches were combined by thermal cross-linking on the surface of a silver electrode in order to develop a MIP-based sensor for the chiral analysis of thyroxine, a thyroid hormone with an amino-acid side chain [53]. The DPASV response peak current was linear to the concentration of thyroxine in the range from 0.010 to 17.2 ng mL" and the achieved detection limit was 0.0060 ng mL. The molecularly Imprinted film displayed absolute enantioselectivity to the template enantiomer and was applied for the determination of thyroxine in aqueous, blood and pharmaceutical samples with no interference from related compounds. 

Chiral Analysis of Amino Acids Biotechnology Applications Clinical Applications Food Applications Pharmaceutical Applications Isotope Separations... 

Figure 50 shows the potential fo packed-column SFC for an efficient and fast control of the chiral purity of pharmaceuticals. Because of the excellent solubility of lipids in supercritical carbon dioxide, SFC in combination with the universal FID detector is a very helpful tool in lipid analysis. 

In the chiral analysis of many drugs, pharmaceuticals and agrochemicals by HPLC, detection is mostly achieved using the UV mode [1-7], and hence this detection mode has also been used for the chiral resolution of some environmental pollutants [8], However, some organochlorine pollutants are transparent to UV radiation hence, the UV detection mode is not suitable and some other detection devices have to be used in chiral HPLC, the most of which are MS, optical detectors and so on. 

Various approaches to chiral resolution have been developed for the analysis of pharmaceuticals and drugs but, unfortunately, few reports and monographs are available on the chiral separation of pollutants. Therefore, we have set out to write this book, which deals with the distribution, toxicities and art of analysis of chiral pollutants by gas chromatography and liquid chromatography that is, by high performance liquid chromatography (HPLC), sub- and supercritical fluid chromatography (SFC),... 

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