title: Development and validation of a stereoselective liquid chromatography-tandem mass spectrometry assay for quantification of S- and R-metoprolol in human plasma.
abstract: A stereoselective liquid chromatography-tandem mass spectrometry assay was developed and validated for quantification of S- and R-metoprolol at concentrations of 0.5-50 microg/L in human plasma. Metoprolol was extracted from plasma by liquid-liquid extraction with ethyl acetate (82% recovery). Chromatographic separation of the enantiomers was achieved on a chiral Chirobiotic T column using an isocratic mobile phase consisting of methanol/acetic acid/ammonia (100/0.15/0.15, v/v/v). An ion trap mass spectrometer with an electrospray interface was used for detection in the positive mode, monitoring the m/z transition 268-->191 for metoprolol. Standard curves for S- and R-metoprolol fitted quadratic functions (r(2)>or=0.9995) over the range 0.5-50 microg/L in plasma, with 0.5 microg/L representing the limit of quantification. In this range, relative standard deviations were <6% for intra-day precision and <10% for inter-day precision. The accuracy was within the range of 92-105%.
authors.affiliation: Clinical Pharmacology, Department of Medicine, University of Otago, Christchurch, New Zealand. berit.jensen@cdhb.govt.nz
authors.forename: Berit P
authors.initials: BP
authors.lastname: Jensen
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Sharp
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Gardiner
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Begg
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008790:Metoprolol / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol