Deep eutectic solvents combined with beta-cyclodextrin derivatives for chiral separation of typical adrenergic receptor agonists by capillary electrophoresis with amperometric detection

Enantioseparation has always been one of the research hotspots and difficulties in the field of modern separation science. In this work, a binary chiral electrophoretic separation system was constructed using deep eutectic solvents (DESs) coupled with beta-cyclodextrin derivatives based on capillary electrophoresis with amperometric detection system, and five groups of typical adrenergic receptor agonists (adrenaline, salbutamol, isoproterenol, norepinephrine and terbutaline) were selected as the model enantiomers. The effects of additive types and contents of DESs and cyclodextrins, and the pH value and concentration of the running buffer on the resolution of the selected chiral compounds were investigated in detail. The mechanism of DESs improving separation was explored preliminarily by means of UV spectrophotometry, which was further verified based on the comparison of single and mixed components of choline chlorine-urea DES. Under the optimum conditions, the relative standard deviations for inter-day and intra-day repeatability of the migration time, peak area and resolution for adrenaline and salbutamol were within 8.7%, and the limits of detection reached 0.030 mu g mL(-1) (S/N = 3). The recovery data were in the range of 96.3-118.7%. The developed methods have been applied for the analyses of (+)-adrenaline hydrochloride injection and (+/-)-salbutamol aerosol. This binary chiral electrophoretic separation system by CE-AD has high detection sensitivity and low analytical cost, providing an alternative for the separation and analysis of chiral drugs.

Automated summary

Enantioseparation of adrenergic receptor agonists using a binary chiral electrophoretic separation system based on deep eutectic solvents (DESs) and cyclodextrin derivatives was investigated. The effects of solvent and buffer conditions on resolution were studied, and the mechanism of DESs enhancing separation was explored. The developed methods showed high sensitivity and accuracy and were successfully applied for the analysis of chiral drugs.