title: Stereospecific gas chromatographic/mass spectrometric assay of the chiral labetalol metabolite 3-amino-1-phenylbutane.
abstract: We previously identified 3-amino-1-phenylbutane (APB) as an oxidative N-dealkylated, metabolite of the antihypertensive agent labetalol. Labetalol has two asymmetric centers and is used clinically as a mixture of the four possible stereoisomers; APB has one asymmetric center. We now report an enantiospecific gas chromatographic/mass spectrometric assay for APB in urine. After adding the internal standard 1-methyl-2-phenoxyethylamine and alkalinizing, the urine samples were extracted with ether. The extracts were derivatized with the optically active acid chloride prepared from (S)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid. The derivatives were separated by capillary gas chromatography and detected by electron capture negative ion chemical ionization mass spectrometry with selected ion monitoring. The derivative of the R enantiomer eluted first, and the [M--32]- ions were monitored for both the drug and the internal standard. The method was linear in the 0.05-2.5 micrograms enantiomer-1 ml-1 range and had inter-assay and intra-assay coefficients of variation of less than 6%. The assay was used in the analysis of urine samples from a patient in labetalol therapy and no interference was found. Further studies are needed to elucidate the oxidative metabolism of labetalol and its stereochemical aspects.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver 80262.
authors.forename: A
authors.initials: A
authors.lastname: Changchit
authors.forename: J
authors.initials: J
authors.lastname: Gal
authors.forename: J A
authors.initials: JA
authors.lastname: Zirrolli
mesh_terms: D000328:Adult; D002082:Butylamines / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007741:Labetalol / Q000378:metabolism*; D008297:Male
chemical_list: D002082:Butylamines; C058063:3-amino-1-phenylbutane; D007741:Labetalol