Development of an enantioselective capillary electrophoretic method for the simultaneous determination of montelukast enantiomeric and diastereoisomeric forms and its main degradation product

Abstract

A stereoselective CD-MEKC system has been developed for the quality control of Montelukast(MK), commercialized as a pure enantiomer. The proposedmethod is the first onethat allows the simultaneous determination ofMK, its enantiomeric form, diasteroisomersand its main degradation compound (MK sulphoxide). CD-MEKC system is composed of10 mM SDS, 10 mM sulfobutylether--CD, 10 mM TM--CD, and 20 mM borate bufferat pH 9.0. Combination of these two CDs allows high baseline enantioresolution betweenMK and its enantiomeric impurity, but also, between the diasteroisomeric forms. Moreover,a multivariate design was applied to optimize operational parameters. The methodwas designed to meet with requirements of the official pharmacopoeias and fully validatedaccording to international guidelines. Linearity ofMKwas demonstrated in the range from10.0 to 100.0 g/mL (r2 = 0.9908) with a LOD and LOQ of 0.30 and 0.90 g/mL, respectively.Intra and interday precision were evaluated and RSD values were below 2%, andalso, accuracy expressed as percentage of recovery was in a range from 99.0 to 101.9 for thethree assayed levels. The method allows determining 0.02% w/w of the enantiomeric anddiasteroisomeric impurities, and 0.01% w/w ofMK sulphoxide. Robustness was evaluatedby a Plackett and Burman design. Finally, the CD-MEKC system was successfully appliedto the determination of related substances in MK bulk drug and its quantification in twopediatric pharmaceutical dosage forms.