title: Rapid chiral separation of atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid using supercritical fluid chromatography-tandem mass spectrometry - Application to wetland microcosms.
abstract: A method for enantiomeric separation of the three β-blocking agents atenolol, metoprolol, propranolol and the zwitterionic metoprolol acid, a major metabolite of both metoprolol and in environmental matrices also atenolol, has been developed. By use of supercritical fluid chromatography and the polysaccharide-based Chiralpak(®) IB-3, all four compounds were simultaneously enantiomerically separated (Rs>1.5) within 8min. Detection was performed using tandem mass spectrometry, and to avoid isobaric interference between the co-eluting metoprolol and metoprolol acid, the achiral column Acquity(®) UPC(2) BEH 2-EP was attached ahead of to the chiral column. Carbon dioxide with 18% methanol containing 0.5% (v/v) of the additives trifluoroacetic acid and ammonia in a 2:1 molar ratio were used as mobile phase. A post column make-up flow (0.3mL/min) of methanol containing 0.1% (v/v) formic acid was used to enhance the positive electrospray ionization. Detection was carried out using a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode, using one transition per analyte and internal standard. The method was successfully applied for monitoring the enantiomeric fraction change over time in a laboratory scale wetland degradation study. It showed good precision, recovery, sensitivity and low effect of the sample matrix.
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Alfred
authors.initials: A
authors.lastname: Svan
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC Box 574, SE-751 23 Uppsala, Sweden; National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, SE-751 89 Uppsala, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hedeland
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC Box 574, SE-751 23 Uppsala, Sweden; Medical Products Agency, Box 26, SE-751 03 Uppsala, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Arvidsson
authors.affiliation: Department of Civil & Environmental Engineering, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Jasper
authors.affiliation: Department of Civil & Environmental Engineering, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Sedlak
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC Box 574, SE-751 23 Uppsala, Sweden. Electronic address: Curt.Pettersson@farmkemi.uu.se.
authors.forename: Curt E
authors.initials: CE
authors.lastname: Pettersson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis*; D001262:Atenolol / Q000032:analysis*; D025924:Chromatography, Supercritical Fluid / Q000379:methods; D008790:Metoprolol / Q000032:analysis*; D011433:Propranolol / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods; D014874:Water Pollutants, Chemical / Q000032:analysis*; D053833:Wetlands
chemical_list: D000319:Adrenergic beta-Antagonists; D014874:Water Pollutants, Chemical; D001262:Atenolol; D011433:Propranolol; D008790:Metoprolol
keywords: Chiralpak IB-3; Enantiomeric separation; Metoprolol acid; SFC–MS; UPC2; Wetland microcosm