Pool W F, Crooks P A
Drug Metab Dispos. 1985 Sep-Oct;13(5):578-81.
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.
在豚鼠体内研究了甲基化尼古丁代谢物R-(+)-[14C-NCH3]N-甲基烟碱乙酸盐的体内生物转化和组织分布。腹腔注射后24小时尿液代谢物的检测和定量通过与放射化学流通检测器相连的阳离子交换高效液相色谱法进行。尿液代谢物谱由五个峰组成。一个峰在接近空体积处洗脱，三个峰与N-甲基可替宁离子、N-甲基去甲烟碱离子和N-甲基烟碱离子的标准品共洗脱。还检测到了第五种尚未鉴定的代谢物。24小时后14C标记在肾上腺和附睾中的组织分布最高，其次是胆囊、膀胱、肾脏、脾脏和心脏。在大脑中未发现大量的14C。结果表明，在豚鼠R-(+)-尼古丁代谢过程中，N-甲基可替宁离子和N-甲基去甲烟碱离子都是在N-甲基烟碱离子形成之后形成的。
