Stereospecific in vivo N-methylation of nicotine in the guinea pig

Abstract

R-(+)-[3H-N'-CH3]N-methylnicotinium ion has been identified as a urinary metabolite of ip administered R-(+)-[3H-N'-CH3]nicotine in the guinea pig. Under similar conditions, S-(-)-[3H-N'-CH3]nicotine is not converted to the corresponding N-methylated metabolite. R-(+)-N-methylnicotinium salt was isolated from the urine of guinea pigs that had been chronically dosed ip with R-(+)-nicotine. The identification and stereochemical analysis of this metabolite were carried out using analytical and preparative cation exchange high pressure liquid chromatography and chemical reduction followed by GLC-mass spectrometric analysis and 1H NMR spectroscopy. The results show that nicotine is stereospecifically biotransformed into an N-methylated urinary metabolite in the guinea pig.