Simultaneous determination of propafenone and 5-hydroxypropafenone enantiomers in plasma by chromatography on an amylose derived chiral stationary phase
Lrp. De Abreu et al., Simultaneous determination of propafenone and 5-hydroxypropafenone enantiomers in plasma by chromatography on an amylose derived chiral stationary phase, J PHARM B, 20(1-2), 1999, pp. 209-216
An enantioselective liquid chromatography method was developed for the simu
ltaneous determination of propafenone (PPF) and 5-hydroxypropafenone (PPF-5
OH) enantiomers in plasma. After liquid-liquid extraction with dichlorometh
ane, the enantiomers were resolved on a Chiralpak AD column using hexane-et
hanol (88:12, v/v) plus 0.1% diethylamine as the mobile phase and monitored
at 315 nm. Under these conditions the enantiomeric fractions of the drug a
nd of its metabolite were analysed within 20 min. The extraction procedure
resulted in absolute recoveries of 62.9 and 61.3% for (R)- and (S)-PPF, res
pectively, and of 57.6 and 56.5% for (R)- and (S)-PPF-5OH, respectively. Th
is procedure was efficient in removing endogenous interferents as well the
interference of an other PPF metabolite, N-despropylpropafenone (PPF-NOR).
The calibration curves were linear over the concentration range 25-1250 ng/
ml. Low values of the coefficients of variation were demonstrated for both
within-day and between day assays. The method described in this paper allow
s the determination of PPF and PPF-5OH enantiomers at plasma levels as low
as 25 ng/ml and can be used in clinical pharmacokinetic studies. (C) 1999 E
lsevier Science B.V. Al rights reserved.