Use of choline chloride-D-sorbitol deep eutectic solvent as additive in cyclodextrin-electrokinetic chromatography for the enantiomeric separation of lacosamide

The potential of chiral deep eutectic solvents to enhance the chiral discrimination in Cyclodextrin-Electrokinetic Chromatography is demonstrated in this work. With this aim, a method enabling the enantiomeric separation of the antiepileptic drug lacosamide was developed. After a screening using 12 cyclodextrin derivatives, succinyl-beta-CD was chosen due to its higher discrimination power to separate lacosamide enantiomers. The effect of different variables, such as cyclodextrin concentration, buffer concentration, temperature and separation voltage, on the enantiomeric separation of lacosamide, was studied. As the maximum enantiomeric resolution achieved under the optimized conditions was lower than 1.5, the effect of the addition of methanol or different deep eutectic solvents (choline chloride - ethylene glycol, choline chloride - urea, choline chloride - D-glucose, and choline chloride - D-sorbitol) as additives to the separation medium was investigated. The best results in terms of enantiomeric resolution and analysis time were obtained using choline chloride - D-sorbitol at a 0.5% (w/v) in a 100 mM borate buffer (pH 9.0) with 18 mM succinyl-beta-CD. Under these conditions, lacosamide enantiomers were separated with a resolution value of 2.8. Analytical characteristics of the developed method were evaluated and demonstrated to be adequate to apply the methodology to the enantiomeric analysis of lacosamide in a pharmaceutical formulation.

Automated summary

The study demonstrated the potential of chiral deep eutectic solvents in enhancing chiral discrimination in Cyclodextrin-Electrokinetic Chromatography. A method for enantiomeric separation of the antiepileptic drug lacosamide was developed using succinyl-beta-CD as the optimal cyclodextrin derivative. By studying various variables, the addition of choline chloride - D-sorbitol was found to provide the best results with an enantiomeric resolution of 2.8 for lacosamide enantiomers.