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