Characterization of the stereoselective metabolism of thiopental and its metabolite pentobarbital via analysis of their enantiomers in human plasma by capillary electrophoresis
S. Zaugg et al., Characterization of the stereoselective metabolism of thiopental and its metabolite pentobarbital via analysis of their enantiomers in human plasma by capillary electrophoresis, J CHROMAT A, 838(1-2), 1999, pp. 237-249
Using capillary zone electrophoresis (CZE) with a 75 mM phosphate buffer at
pH 8.5 containing 5 mM hydroxypropyl-gamma-cyclodextrin (OHP-gamma-CD) as
chiral selector, the separation of the enantiomers of thiopental and its ox
ybarbiturate metabolite, pentobarbital, is reported. Enantiomer assignment
was performed via preparation of enantiomerically enriched fractions using
chiral recycling isotachophoresis (rITP) processing of racemic barbiturates
and analysis of rITP fractions by chiral CZE and circular dichroism spectr
oscopy. Thiopental and pentobarbital enantiomers in plasma were extracted a
t low pH using dichloromethane and extracts were reconstituted in acetonitr
ile or 10-fold diluted, achiral running buffer. The stereoselectivity of th
e thiopental and pentobarbital metabolism was assessed via analysis of 12 p
lasma samples that stemmed from patients undergoing prolonged or having com
pleted long-term racemic thiopental infusion. The data obtained revealed a
modest stereoselectivity with R-(+)-thiopental /S-(-)-thiopental and R-(+)-
pentobarbital /S-(-)-pentobarbital plasma ratios being <1 (P <0.05 compared
to data obtained with racemic controls) and >1 (P < 0.001), respectively.
The total S-(-)-thiopental plasma concentration was found to be on average
about 248 higher compared to the concentration of R-(+)-thiopental, whereas
the total R-(+)-pentobarbital plasma level was observed to be on average 2
9% higher compared to the S-(-)-pentobarbital concentration. (C) 1999 Elsev
ier Science B.V. All rights reserved.