Effect of deep eutectic solvents on the enantiomeric separation of mirabegron by cyclodextrin-electrokinetic chromatography. Application to the analysis of pharmaceutical and biological matrices

The growing interest in green chemistry and environmentally friendly analytical methods has driven the search for alternative solvents capable of enhancing chiral separations. In this context, this work focuses on evaluating the effect of deep eutectic solvents (DESs) to enhance the enantiomeric separation of mirabegron, a drug used to treat overactive bladder, by Electrokinetic Chromatography. Two DESs (Tetrabutylammonium bromide-Citric acid (TBABr-CA) and Choline chloride-Citric acid (ChCl-CA)) were synthesized and characterized. After a screening to select β-cyclodextrin sulfobutyl ether sodium salt (Captisol) as the most appropriate cyclodextrin (CD) to perform the chiral analysis of mirabegron, the potential of these two DESs to increase the enantiomeric separation was evaluated. The addition of ChCl-CA to the separation medium resulted in an enhancement in the enantioseparation compared to that obtained using only the CD. Employing a 50 mM phosphate buffer (pH 3.0) containing 1.25% ( w / v ) Captisol and 2.0% (w/v) ChCl-CA, mirabegron enantiomers were separated with a resolution value of 2.0 in less than 12 min. After evaluating the analytical characteristics of the developed methodology, it was successfully applied to the quality control of an enantiopure pharmaceutical formulation and the determination of mirabegron enantiomers in urine samples.