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Stereoselective Analysis of Flecainide Enantiomers Using Reversed-Phase Liquid Chromatography for Assessing CYP2D6 Activity

Stereoselective Analysis of Flecainide Enantiomers Using Reversed-Phase Liquid Chromatography for Assessing CYP2D6 Activity

Kosuke Doki, Yukio Sekiguchi, Keisuke Kuga, Kazutaka Aonuma, Yukinao Kohda, Masato Homma

Biomed Chromatogr. 2014 Sep;28(9):1193-8.

PMID: 24523024

Abstract:

Stereoselective analyses of flecainide enantiomers were performed using reversed-phase high-performance liquid chromatography (HPLC) equipped with a polysaccharide-based chiral column (Chiralpak AS-RH) and fluorescence detector. Excitation and emission wavelengths were set at 300 and 370 nm, respectively. Flecainide enantiomers in serum and urine were extracted using diethyl ether. The mobile phase solution, comprising 0.1 m potassium hexafluorophosphate and acetonitrile (65:35, v/v), was pumped at a flow rate of 0.5 mL/min. The recoveries of flecainide enantiomers were greater than 94%, with the coefficients of variation (CVs) <6%. The calibration curves of flecainide enantiomers in serum and urine were linear in the concentration range 5-500 ng/mL and 0.75-15 µg/mL (r > 0.999), respectively. CVs in intra-day and inter-day assays were 1.8-5.8 and 3.4-7.5%, respectively. In a pharmacokinetic study, the ratios of (S)- to (R)-flecainide (S/R ratio) in the area under the curve and the amount of flecainide enantiomers excreted in urine were lower in a subject carrying CYP2D6*10/*10 than in subjects carrying CYP2D6*1/*2. The S/R ratio of trough serum flecainide concentration ranged from 0.79 to 1.16 in patients receiving oral flecainide. The present HPLC method can be used to assess hepatic flecainide metabolism in a pharmacokinetic study and therapeutic drug monitoring.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP54143554	(±)-Flecainide solution		54143-55-4	Price

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