Evaluation of clarithromycin lactobionate as a novel chiral selector for enantiomeric separation of basic drugs in capillary electrophoresis

Abstract

Nowadays, macrocyclic antibiotics are presenting an increasing number of enantioseparation applications. The macrocyclic antibiotics used as chiral selectors in capillary electrophoresis (CE) include the ansamycins and the glycopeptides. The macrolides, another important class of macrocyclic antibiotics, have been reported as a new type of chiral selectors recently. In this study, clarithromycin lactobionate (CL), belonging to the group of macrolide antibiotics, was first investigated for its potential as a novel chiral selector in CE for enantiomeric separation of several basic drugs. As observed, CL allowed excellent separation of the enantiomers of metoprolol, atenolol, propranolol, bisoprolol, esmolol, ritodrine, and amlodipine, as well as partial enantioresolution of labetalol and nefopam. In addition, CL possesses advantages such as high solubility and low viscosity in the solvent and very weak UV absorption. In the course of this study, it was found that both migration times and enantioseparation of the basic drugs were influenced by several experimental parameters, e.g. selector concentration, the composition and pH of the BGE, the type and concentration of organic modifier, and applied voltage. Thus, the effects of these factors were systematically investigated, and satisfactory enantioseparations of the studied drugs were achieved at the buffer pH range of 7.3-7.5 using 12.5 mM borax buffer with 50% v/v methanol, 60 mM CL, and 20 kV applied voltage. Moreover, comparison of the influences of the studied parameters was further investigated by means of Statistical Product and Service Solutions (SPSS) in this article.

Lactobionic acid: A high value-added lactose derivative for food and pharmaceutical applications

“…Pharmaceutical Enhancement of solubility of macrolide antibiotics such as erythromycin and clarithromycin Anti-aging and keratinizing ingredient of skin care cosmetics Calcium supplementation Metal-chelating agent in organ preservation solutions Ingredient in chlorhexidine-based disinfectant Bio-surfactant in its fatty acid derivatives forms Inducer for cellulase production by Trichoderma reesei Functional molecule in the synthesis of polymeric nanoparticles for liver-specific drug deliver (Ahamed & Vermette, 2008;Frutos et al, 1997;Green et al, 2009;Jain & Jain, 2010;Playne & Crittenden, 2009;Van Hecke et al, 2011) Food Acidulant with a sweet taste Filler in cheese production Firming agent Calcium carrier in functional drinks Reduction of souring and ripening time for the production of cheese and yogurt Enhancement of flavors Improvement of bitter or sour taste of foods Preservation of aroma freshness Preparation of dairy products with reduced lactose content (Gerling, 1998;Merrill & Singh, 2009;Nakano et al, 2010;Nordkvist et al, 2007;Playne & Crittenden, 2009) Chemical Ion sequestrant in detergent solutions Biodegradable cobuilder in washing powder Anti-corrosive coatings Chiral selector for enantiomeric separation of basic drugs in capillary electrophoresis (clarithromycin lactobionate) Reactant for synthetic amides (Gerling, 1998;Yu et al, 2011) Nanotechnology Part of biocompatible scaffolds for tissue engineering Part of nanoplatforms for new bioimaging applications Ingredient of galactose-conjugated fluorescent nanoparticles for immunofluorescence assays (Chung et al, 2002;Kekkonen et al, 2009;Peng et al, 2007) volunteers periodically over two weeks (Tasic-Kostov et al, 2010). LBA could increase the synthesis of glycosaminoglycans in the skin, and it has been shown to enhance cell turnover in vitro (Briden & Green, 2005).…”

Chiral selectors in CE: Recent developments and applications

“…It is important to mention that, in comparison to CZE, this was the first study that was reported on the use of a macrocyclic antibiotic as a CS in NACE. Two more macrolide antibiotics, clarithromycin lactobionate and azithromycin, have also been recently investigated as new CSs in CE by Chen's group and by Kumar and Park , respectively. Both CSs proved to have high potential over the enantioseparation of basic drugs.…”

Study on the Extraction Kinetics of Ketoconazole with Hydroxypropyl-β-Cyclodextrin as a Selector

“…With the growing demand of enantiomerically pure compounds in pharmaceutical industry and chemical industry , the development of new competitive separation technologies is inevitable. In the past few decades, some separation methods have been developed widely including diastereomeric crystallization , chromatographic techniques , extraction , capillary electrophorsis (CE) , and liquid membrane . Since the low versatility and complicated postprocess in crystallization, the limited mass transfer rate in membrane technology and additionally the poor reproducibility in CE, enantioseparation by liquid–liquid extraction with a specific chiral extractant can be considered as a promising alternative, which is lower cost, more versatility, and easier for scale‐up.…”