Resolution of enantiomers of the antiarrhythmic drug encainide and its major metabolites by chiral derivatization and high-performance liquid chromatography

Journal of Chromatography
C PrakashR F Mayol

Abstract

Commercially available chiral columns were unable to provide adequate resolution of enantiomers of the antiarrhythmic drug encainide or its major metabolites. The homochiral derivatizing agent, (-)-menthyl chloroformate, was found to react at the tertiary piperidine nitrogen of racemic encainide providing two menthyl carbamate diastereomers. The individual diastereomers could be separated with baseline resolution on normal-phase high-performance liquid chromatography on a silica column. Structures of the derivatives were confirmed by electron impact mass spectrometry and 1H NMR spectroscopy. The method was adapted for the chiral analysis of the major metabolites of encainide. The limit of sensitivity for racemic encainide was 10 ng on column and it was possible to detect a mixture containing (+)- and (-)-encainide in a ratio of 1:99. Preliminary studies indicated that (-)-encainide was O-demethylated to a greater extent than the (+)-enantiomer by rat liver microsomes.

References

May 1, 1986·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C B McAllisterG R Wilkinson
Mar 1, 1986·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·B Testa

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Citations

Oct 1, 1992·Journal of Clinical Pharmacology·F M Pasutto
Sep 23, 1994·Journal of Chromatography. B, Biomedical Applications·S Görög, M Gazdag
Sep 1, 1999·The Journal of Pharmacy and Pharmacology·H FarsamN Gharavi

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