Enantioselective determination of metoprolol acidic metabolite in plasma and urine using liquid chromatography chiral columns: applications to pharmacokinetics.
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.
Cerqueira
Paula Macedo
PM
Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, SP, São Paulo, Brazil.
Boralli
Vanessa Bergamin
VB
Coelho
Eduardo Barbosa
EB
Lopes
Norberto Peporine
NP
Guimarães
Luis Fernando Lopes
LF
Bonato
Pierina Sueli
PS
Lanchote
Vera Lucia
VL
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
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol