RT Journal Article
SR Electronic
T1 Biotransformation of primary nicotine metabolites. I. In vivo metabolism of R-(+)-[14C-NCH3]N-methylnicotinium ion in the guinea pig.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 578
OP 581
VO 13
IS 5
A1 W F Pool
A1 P A Crooks
YR 1985
UL http://dmd.aspetjournals.org/content/13/5/578.abstract
AB The in vivo biotransformation and tissue distribution of the methylated nicotine metabolite R-(+)-[14C-NCH3]N-methylnicotinium acetate was studied in the guinea pig. The detection and quantification of 24-hr urinary metabolites after ip injection was determined by cation-exchange HPLC interfaced to a radiochemical flowthrough detector. The urinary metabolite profile consisted of five peaks. One eluted close to the void, and three coeluted with authentic standards of N-methylcotininium ion, N-methylnornicotinium ion, and N-methylnicotinium ion. A fifth, and as yet unidentified, metabolite was also detected. Tissue distribution of 14C label after 24 hr was highest in the adrenal gland and epididymis followed by the gallbladder, bladder, kidney, spleen, and heart. No significant amounts of 14C were found in the brain. The results indicate that N-methylcotininium ion and N-methylnornicotinium ion are both formed subsequent to the formation of N-methylnicotinium ion in the metabolism of R-(+)-nicotine in the guinea pig.