Enantioselective analysis of metoprolol in plasma using high-performance liquid chromatographic direct and indirect separations: applications in pharmacokinetics

Citation
Vl. Lanchote et al., Enantioselective analysis of metoprolol in plasma using high-performance liquid chromatographic direct and indirect separations: applications in pharmacokinetics, J CHROMAT B, 738(1), 2000, pp. 27-37
Citations number
30
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF CHROMATOGRAPHY B
ISSN journal
13872273 → ACNP
Volume
738
Issue
1
Year of publication
2000
Pages
27 - 37
Database
ISI
SICI code
1387-2273(20000128)738:1<27:EAOMIP>2.0.ZU;2-Z
Abstract
Direct enantioselective separation on chiral stationary phases and indirect separation based on the formation of diastereomeric derivatives were devel oped and compared for the HPLC analysis of R(+) and S(-)-metoprolol in huma n plasma. Plasma samples prepared using solid-phase extraction columns or l iquid-liquid extraction were directly analyzed on a Chiralpack(R) AD or on a Chiralcel(R) OD-H columns, respectively S-(-)-menthyl choroformate was al so used to yield diastereomeric derivatives resolved on a RP-g column. The methods were employed to determine plasma concentrations of metoprolol enan tiomers in a pharmacokinetic study of single dose administration of racemic metoprolol to a healthy Caucasian volunteer phenotyped as extensive metabo lizer of debrisoquine. The correlation coefficients among enantioselective metoprolol plasma concentrations (5-223 ng/ml) obtained by the three method s were equal or higher than 0.99. The direct method that employed the chira l column Chiralpak(R) AD may be considered the most sensitive, although the three methods demonstrated interchangeable use in the pharmacokinetic inve stigation. (C) 2000 Published by Elsevier Science B.V. All rights reserved.