Determination of enantiomeric excess by capillary electrophoresis

Abstract

Capillary electrophoresis (CE) is becoming an established method for the determination of chiral trace impurities. This paper provides an overview of the state of the art of CE for such determinations. Detection limits of 0.1% impurity is widely accepted as a minimum requirement for chiral trace impurity determinations. This can be relatively easily achieved with CE. However, determination of lower concentrations requires careful optimization of the separation system. Four factors that are of particular significance for trace enantiomeric determinations: resolution, limit of detection, linear range and type of detection, are discussed. Further, the advantages and disadvantages of derivatization in this context are treated as well as the separation approach, ie., direct chiral separation or separation after the formation of diastereomers. It is concluded that the limit of impurity detection can be about 0.05% when UV detection is employed. Using laser-induced fluorescence detection, a quantitative determination at the 0.005% level is often possible.

Sensitive chiral analysis by capillary electrophoresis

“…These thresholds have recently been revised (February 2002 and establishing that for drug substances where the maximum daily dose (MDD) is 2 g/day or below, impurities must be reported if they are present above 0.05%, identified if above 0.10%, and qualified if above 0.15%. Obviously, to accomplish these requirements the sensitivity of detection has to be taken into consideration [1][2][3]. On the other hand, the determination of chiral compounds in biological samples (plasma, urine, cerebrospinal fluid, tissues, cells, etc.)…”

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

“…The retention or migration orders of the enantiomers are a very important factor in the determination of trace impurities [34,35]. The tailing of the major peak can mask that of the minor compounds if the minor is coming later.…”

Pharmaceutical and biomedical applications of chiral capillary electrophoresis and capillary electrochromatography: An update

“…While the enantiomeric purity, or enantiomeric excess (ee) is often used as measure in chemical synthesis, an enantiomeric impurity (ei) is usually quantified in analytical chemistry [12,75]. Assuming an impurity with S-configuration the enantiomeric impurity is defined as:…”

“…The quantitation of the enantiomers may be based on calibration curves but as pure standards are not always available the determination is often carried out via the normalization method and reported as percent of the area ratios. The use of CE for the determination of the enantiomeric excess has been highlighted [75,76].…”