STEREOSPECIFIC INVIVO N-METHYLATION OF NICOTINE IN THE GUINEA-PIG

  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (2) , 175-185
Abstract
R-(+)-[3-N''-CH3]N-methylnicotinium ion was identified as a urinary metabolite of i.p. 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 were chronically dosed i.p. 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. Evidently, nicotine is stereospecifically biotransformed into an N-methylated urinary metabolite in the guinea pig. [Work in this laboratory has recently focused on the possible involvement of methylated nicotine metabolites in the toxicology of tobacco products.].