Produção Nacional
Revisado por pares
Enantioselective determination of metoprolol acidic metabolite in plasma and urine using liquid chromatography chiral columns: applications to pharmacokinetics
2002; Elsevier BV; Volume: 783; Issue: 2 Linguagem: Inglês
10.1016/s1570-0232(02)00705-5
ISSN1873-376X
AutoresPaula Macedo Cerqueira, Vanessa Bergamin Boralli, Eduardo Barbosa Coelho, Norberto Peporine Lopes, Luís Fernando Lopes Guimarães, Pierina Sueli Bonato, Vera Lúcia Lanchote,
Tópico(s)Antibiotics Pharmacokinetics and Efficacy
ResumoEnantioselective 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 μg 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.
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