title: 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 proposed method is the first one that allows the simultaneous determination of MK, its enantiomeric form, diasteroisomers and its main degradation compound (MK sulphoxide). CD-MEKC system is composed of 10 mM SDS, 10 mM sulfobutylether-β-CD, 10 mM TM-β-CD, and 20 mM borate buffer at pH 9.0. Combination of these two CDs allows high baseline enantioresolution between MK and its enantiomeric impurity, but also, between the diasteroisomeric forms. Moreover, a multivariate design was applied to optimize operational parameters. The method was designed to meet with requirements of the official pharmacopoeias and fully validated according to international guidelines. Linearity of MK was demonstrated in the range from 10.0 to 100.0 μg/mL (r(2) = 0.9908) with a LOD and LOQ of 0.30 and 0.90 μg/mL, respectively. Intra and interday precision were evaluated and RSD values were below 2%, and also, accuracy expressed as percentage of recovery was in a range from 99.0 to 101.9 for the three assayed levels. The method allows determining 0.02% w/w of the enantiomeric and diasteroisomeric impurities, and 0.01% w/w of MK sulphoxide. Robustness was evaluated by a Plackett and Burman design. Finally, the CD-MEKC system was successfully applied to the determination of related substances in MK bulk drug and its quantification in two pediatric pharmaceutical dosage forms.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Flor
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Martin
authors.initials: M
authors.lastname: Huala Juan
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tripodi
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. slucangi@ffyb.uba.ar.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. slucangi@ffyb.uba.ar.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lucangioli
mesh_terms: D000085:Acetates / Q000032:analysis*; D003521:Cyclopropanes; D019075:Electrophoresis, Capillary / Q000379:methods*; D020024:Leukotriene Antagonists / Q000032:analysis*; D057230:Limit of Detection; D011804:Quinolines / Q000032:analysis*; D012015:Reference Standards; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013440:Sulfides
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast
keywords: Capillary electrophoresis; Cyclodextrins; Montelukast; Stereoselective analysis