title: Development and validation of a sensitive LC-MS/MS method for the determination of fenoterol in human plasma and urine samples.
abstract: Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen), a rapid LC-MS/MS method was developed for the determination of (R,R')-Fen and (R,R';S,S')-Fen in plasma and urine. The method was fully validated and was linear from 50pg/ml to 2000pg/ml for plasma and from 2.500ng/ml to 160ng/ml for urine with a lower limit of quantitation of 52.8pg/ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R')-Fen and (S,S')-Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R')-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R')-Fen and (R,R';S,S')-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S')-Fen reduces the sulfation of the active (R,R')-Fen. The data suggest that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active (R,R')-Fen for use in the treatment of cardiovascular disease.
authors.affiliation: Laboratory of Clinical Investigation, Division of Intramural Research Programs, National institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sanghvi
authors.forename: A
authors.initials: A
authors.lastname: Ramamoorthy
authors.forename: J
authors.initials: J
authors.lastname: Strait
authors.forename: I W
authors.initials: IW
authors.lastname: Wainer
authors.forename: R
authors.initials: R
authors.lastname: Moaddel
mesh_terms: D000322:Adrenergic Agonists / Q000097:blood* / Q000737:chemistry / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005280:Fenoterol / Q000097:blood* / Q000737:chemistry / Q000652:urine*; D006801:Humans; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000322:Adrenergic Agonists; D005280:Fenoterol
keywords: Bioavailability; Chirobiotic T; Congestive heart failure; β(2)-Adrenergic receptor agonist