title: Enantioselective determination of metoprolol acidic metabolite in plasma and urine using liquid chromatography chiral columns: applications to pharmacokinetics.
abstract: Enantioselective separations on chiral stationary phases with or without derivatization were developed and compared for the HPLC analysis of (+)-(R)- and (-)-(S)-metoprolol acidic metabolite in human plasma and urine. The enantiomers were analysed in plasma and urine without derivatization on a Chiralcel OD-R column, and in urine after derivatization using methanol in acidic medium on a Chiralcel OD-H column. The quantitation limits were 17 ng of each enantiomer/ml plasma and 0.5 microgram of each enantiomer/ml urine using both methods. The confident limits show that the methods are compatible with pharmacokinetic investigations of the enantioselective metabolism of metoprolol. The methods were employed in a metabolism study of racemic metoprolol administered to a patient phenotyped as an extensive metabolizer of debrisoquine. The enantiomeric ratio (+)-(R)/(-)-(S)-acid metabolite was 1.1 for plasma and 1.2 for urine. Clearances were 0.41 and 0.25 l/h/kg, respectively, for the (+)-(R)- and (-)-(S)-enantiomers. The correlation coefficients between the urine concentrations of the acid metabolite enantiomers obtained by the two methods were >0.99. The two methods demonstrated interchangeable application to pharmacokinetics.
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, SP, São Paulo, Brazil.
authors.forename: Paula Macedo
authors.initials: PM
authors.lastname: Cerqueira
authors.forename: Vanessa Bergamin
authors.initials: VB
authors.lastname: Boralli
authors.forename: Eduardo Barbosa
authors.initials: EB
authors.lastname: Coelho
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
authors.forename: Luis Fernando Lopes
authors.initials: LF
authors.lastname: Guimarães
authors.forename: Pierina Sueli
authors.initials: PS
authors.lastname: Bonato
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol