Enantiomeric purity determination of ketoprofen by capillary electrophoresis: development and validation of the method

Abstract

A simple, fast capillary electrophoresis method for determining the total ketoprofen content in an oral pharmaceutical formulation is proposed. The addition of 75 mM of heptakis(tri- O-methyl)-beta-cyclodextrin to the background electrolyte allows the quantitation of the enantiomeric impurity of ( R)-(-)-ketoprofen contained in the formulation. A relative limit of detection is proposed as a measure of the lowest detectable enantiomeric impurity and the results show that the method can detect the minor enantiomer at levels as low as 0.04% in ( S)-(+)-ketoprofen. The chiral method was validated following ICH recommendations and the quality parameters obtained show the suitability of the proposed method. The analysis of samples examined during the course of a stability study under chiral and achiral conditions revealed that the total ketoprofen content did not change significantly with time and the enantiomeric impurity range was 0.1-0.4%.

Enantiomeric impurity determination in capillary electrophoresis using a highly-sulfated cyclodextrins-based method

“…Different optimal conditions were found when the enantiomer impurity was situated either before or after the main compound. Determination of enantiomeric purity is mostly done under overload conditions, which leads to deformed peaks (Magnusson et al, 2002;Blanco et al, 2003), as demonstrated in Fig. 2 cases where the impurity migrates first a better and easier detection and peak integration.…”

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

“…These include the evaluation of the synthetic process [92,94] as well as the analysis of approved drugs [81][82][83][84][85][86][87][88][89][90]. In several cases, the methods not only allowed the determination of the other enantiomer but also of related substances [84,85,92].…”

“…Blanco and co-workers [86] developed and validated an assay for the analysis of (R)-ketoprofen in (S)-ketoprofen. The use of TM-b-CD in an acetate buffer, pH 5.0, allowed the detection of 0.04% of the (R)-enantiomer as impurity.…”

Development and validation of a capillary electrophoresis method for the enantiomeric purity determination of SLV307, a basic potential antipsychotic compound

“…Due to the high efficiency and a large diversity of chiral selectors available at present, CE is a powerful tool for chiral purity determinations of pharmaceuticals during different stages of drug development. Several strategies on method development [2][3][4][5][6][7] as well as validation studies [8][9][10] can be found in literature.…”