Evidence of stereospecificity in the in vivo methylation of [14C] (+/-) -nicotine in the guinea pig
Cundy, K.C.; Godin, C.S.; Crooks, P.A.
Drug Metabolism and Disposition the Biological Fate of Chemicals 12(6): 755-759
1984
ISSN/ISBN: 0090-9556 PMID: 6150826 Document Number: 241889
In vivo metabolism of [14C]nicotine to N-methylnicotinium ion in the guinea pig appears to be a stereospecific biotransformation, involving only the R-(+)-isomer. The detection and quantitation of urinary radiolabeled nicotine metabolites after ip injection of either [N-14CH3](+/-)-nicotine or [2'-14C](+/-)-nicotine, was carried out on an HPLC cation-exchange analytical system. Utilizing the recently discovered phenomenon of differential enantiomeric association, the stereo-chemistry of the methylation pathway was determined. Significant differences in the tissue distribution of 14C label from the [N-14CH3]-vs. [2'-14C]nicotine-treated animals were observed 24 hr after nicotine administration. An unidentified metabolite with high affinity on cation-exchange chromatography, was detected as a metabolite of [2'-14C](+/-)-nicotine, but was not observed as a metabolite of [N-14CH3](+/-)-nicotine.