Stereoisomer Analysis Of β-adrenergic Receptor Blockers In Wasterwater Samples

β-Adrenergic receptor blocker is an important kind of pharmaceuticals mainly used in cardiovascular diseases therapy, which were produced and prescribed mainly as racemates or equal mixtures of enantiomers. The environmental occurrence, transformation and eco-toxicological effect ofβ-blocker enantiomers are potentially different. So it is an urgent need to establish a reliable analytical method for enantiomers determination in wastewater samples so as to study their environmental fate.A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously analysis 16β-blockers (sotalol, atenolol, nadolol, pindolol, acebutolol, metoprolol, celiprolol, labtalol, bisoprolol, carazolol, oxprenolol, betaxolol, propranolol, alprenolol, carvedilol, nebivolol) stereoisomers in sewage. Target compounds in wastewater samples was concentrated and purified by a PCX cartridge, and then separated on a vancomycin-based enantioselective CHIROBIOTICTMⅤcolumn using methanol containing 20 mM ammonium acetate and 0.1% formic acid as mobile phase. As a result, acceptable sepration (R>0.78) could be achieved for chiral enantiomers of all drugs with the multi-reaction monitoring (MRM) mode. The assay for 16β-blockers were linear over the range of 0.05-50μg/L with correlation coefficient (R2)>0.99. Method quantitation limits (MQLs) of target compounds enantiomers in wastewater sample ranged from 0.1 to 1 ng/L. Recoveries of the 16β-blockers (spiked in sewage samples at three concentration levels) ranged over 44.7-122.2%, with relative standard deviations (RSD) no more than 18.7%. This method can be applied in determination of target drugs in wastewater samples.Based on the method above,60 clinical wastewater samples taken from 20 hospitals in Beijing were determined, as well as 20 sewage samples from GBD sewage treatment plant. Thirteen of 16 drugs were detected in these samples, namely atenolol, bisoprolol, metoprolol, propranolol, carazolol, labtalol, sotalol, carvedilol, pindolol, celiprolol, oxprenolol, nebivolol, and acebutolol. The total concentrations of two isomers of the drugs in wastewater samples ranged of 0.2-2669.7 ng/L. Most calculated enantiomer fractions (EF) of detectableβ-blockers were about 0.5. Stereoselective discrepancy might occur during sewage treatment for sotalol. This paper provided analytical-methodological foundation for study ofβ-adrenergic receptor blocker enantiomers in environment.