Simultaneous determination of propafenone and 5-hydroxypropafenone enantiomers in plasma by chromatography on an amylose derived chiral stationary phase

Citation
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
Citations number
16
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
ISSN journal
07317085 → ACNP
Volume
20
Issue
1-2
Year of publication
1999
Pages
209 - 216
Database
ISI
SICI code
0731-7085(199906)20:1-2<209:SDOPA5>2.0.ZU;2-V
Abstract
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.