Micellar liquid chromatography for enantioseparation of β-adrenolytics using (S)-ketoprofen-based reagents

Abstract

ABSTRACTMicellar liquid chromatographic method has been developed for enantioseparation of four β-adrenolytics, namely, (RS)-salbutamol, (RS)-carvedilol, (RS)-bisoprolol, and (RS)-betaxolol. Both sodium docyl sulfate and Brij-35 were used as the surfactants in water as the mobile phase. Advantages for using both the surfactants in combination were investigated. Two (S)-ketoprofen-based activated esters were synthesized by activating its carboxylic group with N-hydroxybenzotriazole and N-hydroxysuccinimide, respectively. The esters were characterized by UV, IR, 1H-NMR, HRMS, and elemental analyses. These reagents were used for the synthesis of diastereomeric derivatives of the chosen β-adrenolytics. These diastereomeric derivatives were enantioseparated on C18 column by high-performance liquid chromatography. Chromatographic conditions were optimized by varying concentration of surfactant and buffer, and pH. The method was validated according to International Conference of Harmonization guideline and the retention factor (k), selectivity factor (α), resolution factor (RS), and limit of detection and limit of quantification were calculated.