Enantioseparation of β-receptor blockers and the enantioselective degradation of carvedilol in soil

Abstract

Enantioseparation of seven β-receptor blockers, including carvedilol, metoprolol, atenolol, sotalol, propafenone, bisoprolol and arotinolol was investigated using HPLC coupled with pre-column derivatization in this work. The derivative conditions of the ratio of the analytes and the derivative reagent, (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, the amount of sodium tetraborate, the reaction temperature and reaction time were optimized. The effects of the types of chromatographic columns, the composition and ratio of the mobile phase and mobile phase additives on enantioseparation were also evaluated in HPLC analysis. The seven pairs of enantiomers showed a good baseline separation on an InfinityLab Poreshell 120 EC-C18 column (150 mm × 4.6 mm, 4 µm) using the mobile phase of methanol and 5 mM ammonium bicarbonate at a flow rate of 1.0 mL/min. In addition, a LC-MS/MS method coupled with QuEChERS extraction for the enantioselective quantitation of carvedilol in soil was developed. The method was fully validated in terms of selectivity, linearity, matrix effect, accuracy, precision, limit of detection and limit of quantification. The linear ranges of carvedilol enantiomers were both 0.5-100 ng/mL and the limits of quantification were 0.5 ng/mL. Extraction recoveries were more than 83.0% with the intra-day and inter-day precision less than 6.8%. The matrix effect values were in the range from 84.5% to 91.3%. The proposed method was successfully applied to determine carvedilol enantiomers in soil and their degradation process was investigated. The degradation of carvedilol enantiomers in soil at natural condition conformed to the first-order degradation kinetics (R² > 0.9790). The half-lives of carvedilol enantiomers were 17.77 and 16.90 days, respectively and the enantiomer fraction (EF) values of carvedilol enantiomers ranged from 0.488 to 0.523 with time in soil, indicating the degradation behaviors, disposition and biotransformation of carvedilol enantiomers in soil showed no enantioselectivity (P > 0.05).

Keywords: Carvedilol; Enantioselective degradation; Enantioseparation; HPLC-MS/MS; QuEChERS; β-blockers.