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Chiral RP-HPLC assay for propafenone enantiomers in rat liver microsomal incubates and its application in vitro metabolism


, : Chiral RP-HPLC assay for propafenone enantiomers in rat liver microsomal incubates and its application in vitro metabolism. Yaoxue Xuebao 35(5): 370-373, May

AIM To separate propafenone enantiomers in rat liver microsomal incubates and investigate probable stereoselectivity in their N-dealkylation. METHODS The concentration of each enantiomer in rat liver microsomal incubates was determined through precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-glucopyranosyl isothiocyanate (GITC), followed by RP-HPLC assay. RESULTS A baseline separation of propafenone enantiomers was achieved on C18-ODS column, with methanol - water - glacial acetic acid (67:33:0.05) as mobile phase. The assay was linear from 0.5 to 320 mugcntdotmL-1 for each enantiomer, and the limit of detection was 100 ngcntdotmL-1. The method affords the average recoveries of 77.1% for R-propafenone and 76.0% for S-propafenone. Stereoselectivity was observed for the phase I metabolism of racemic propafenone in dexamethasone, beta-naphthoflavone induced rat liver microsomal incubates, but not in controls. CONCLUSION The method is simple, cheap and can be applied to study the metabolism of R- and S-propafenone in vitro. Stereoselectivity exists in their N-dealkylation.

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