Investigating the potential of erythromycin and derivatives as chiral selector in capillary electrophoresis

• Published in: Journal of pharmaceutical and biomedical analysis 2004-03, Vol.34 (5), p.861-870
• Main Authors: Thanh Ha, Pham Thi, Van Schepdael, Ann, Roets, Eugène, Hoogmartens, Jos
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Buffers; Capillary electrophoresis; Chiral; Derivatives; Electrophoresis, Capillary - methods; Erythromycin - analogs & derivatives; Erythromycin - analysis; Erythromycin - chemistry; Erythromycins; Fundamental and applied biological sciences. Psychology; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Models, Chemical; Pharmacology. Drug treatments; Selector; Stereoisomerism
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2003.11.004

Macrocyclic antibiotics are present in an increasing number of chiral separation applications. In this study, erythromycin and some derivatives, belonging to the group of macrolide antibiotics, were investigated for their potential as chiral selector. Erythromycin A itself and five related substances namely erythromycin A N-oxide, anhydroerythromycin A, anhydroerythromycin A N-oxide, erythralosamine and erythralosamine N-oxide were included. Twenty-one chiral compounds with a wide difference in physico-chemical properties were used to test the chiral activity of the erythromycins. The chiral compounds were analysed using capillary zone electrophoresis with the erythromycins dissolved in the running buffer at different concentrations ranging from 0.1 to 10mM, with three different BGEs: sodium phosphate pHs 3.0 and 7.0 and sodium borate pH 9.2. The erythromycins showed more interactions with the acidic compounds (as observed with leucovorin, dopa, carbidopa, ketoprofen, indoprofen and warfarin) than with the neutral or weakly basic ones, especially in acidic medium. Unfortunately, no chiral separations were obtained for any of the 21 racemic mixtures. The complexation constants were calculated for the compounds showing interaction, based on the variation of electrophoretic mobility of the compounds in the presence of different concentrations of erythromycins. Finally, the size of erythromycin A was calculated using computational modelling. It was shown that the aglycone ring is only half as big as the β-cyclodextrin cavity, giving a possible explanation for the negative response of erythromycin in this study.