Enantiomeric resolution of 2‐arylpropionic acid nonsteroidal anti‐inflammatory drugs by capillary electrophoresis: Methods and applications

Abstract

The 2-arylpropionic acids (2-APAs) are an important group of nonsteroidal anti-inflammatory drugs. These agents, the majority of which are available as racemates, exhibit stereoselectivity in both their action and disposition. Developments in stereoselective separation science methodology, mainly chromatographic, have facilitated an evaluation of the pharmacological properties of the individual enantiomers of these drugs and contributed to our understanding of both their mode(s) of action and disposition. While a number of electrophoretic techniques, including capillary electrophoresis, capillary electrochromatography and isotachophoresis, have been applied to the stereoselective resolution and stereospecific analysis of these agents using a variety of chiral selectors, e.g., cyclodextrins, oligosaccharides, macrocyclic antibiotics, and proteins, the number of published applications in pharmaceutical and biomedical analysis remains relatively limited. However, the utility of electrophoretic techniques for stereospecific analysis may be illustrated using the 2-APAs as typical examples of chiral acidic pharmaceuticals. Applications include: determination of enantiomeric composition following biosynthetic stereoselective hydrolysis; examination of both achiral and chiral impurity profiles in bulk drugs and formulated products; determination of enantiomeric impurities in both bulk drugs and formulated products; examination of configurational stability following stress testing of formulated products; determination of enantiomeric composition and metabolite profile in biological fluids following administration of the racemates and individual enantiomers. It may be anticipated that future exploitation of electrophoretic approaches to the stereospecific analysis of these agents will result in further contributions to our understanding of their stereoselective biological properties and therapeutic use.

Why not using capillary electrophoresis in drug analysis?

“…Thousands of enantioseparations of chiral drugs have been reported mainly dealing with the influence of the chiral selector such as CDs and various derivatives on the resolution of the isomers [31][32][33][34][35]. However, when it comes to the quantification of the ratio of two isomers or the determination of the enantiomeric excess [36,37], a validation of the method has to be performed.…”

Quantitative Characterization of Derivatization Effects in Separations Techniques, I. Derivatization of Ibuprofen

“…Other derivatives of cyclodextrins have been also applied for chiral separation of ibuprofen in CE [30][31][32][33]. Good separations were achieved using amino substituted permethylated 6-monoamino-6-monodeoxy-β-cyclodextrin and heptakis(2,3-dimethyl-6-amino-6-deoxy)-β-cyclodextrin, because the oppositely charged selectors and selectand can show high resolutions in CE [29].…”

Capillary electrophoresis for the analysis of small‐molecule pharmaceuticals

“…Patel reviewed the use of CE techniques for the enantiomeric resolution of a group of NSAIDs, the 2-arylpropionic acids, with the application to real samples of pharmaceutical and biomedical interest [67]. They concluded that [55,56].…”