Simultaneous determination of propafenone and 5-hydroxypropafenone enantiomers in plasma by chromatography on an amylose derived chiral stationary phase.
An enantioselective liquid chromatography method was developed for the simultaneous determination of propafenone (PPF) and 5-hydroxypropafenone (PPF-5OH) enantiomers in plasma. After liquid liquid extraction with dichloromethane, the enantiomers were resolved on a Chiralpak AD column using hexane-ethanol (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 and 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, respectively, and of 57.6 and 56.5% for (R)- and (S)-PPF-5OH, respectively. This 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 allows 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.
Pires de Abreu
L R
LR
Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-USP, Brazil.
Lanchote
V L
VL
Bertucci
C
C
Cesarino
E J
EJ
Bonato
P S
PS
D000688:Amylose; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008752:Methylene Chloride; D011405:Propafenone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012996:Solutions; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D012996:Solutions; D008752:Methylene Chloride; D011405:Propafenone; C044307:5-hydroxypropafenone; D000688:Amylose