Isolation and analysis of N-oxide metabolites of tertiary amines: quantitation of nicotine-1'-N-oxide formation in mice.
To investigate the formation and elimination of nicotine-1'-N-oxide (NNO) in mice treated with a single injection of nicotine, sensitive and selective methods were developed to quantitate this polar and heat-labile metabolite. The compound was isolated from tissue homogenates as a dodecyl sulfate ion pair with C18 extraction cartridges and analyzed on an amino bonded-phase high-performance liquid chromatographic column with a mobile phase consisting of isopropanol-water. Overall recoveries of NNO were 64-76% from biological media. Several methods of detection were evaluated; radiolabeling was necessary to achieve the sensitivity required for pharmacokinetic studies in mice. The cis and trans isomers of NNO were separated on a Partisil PAC column and enzymatic selectivity was evaluated for the formation of these isomers in mice.
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D008099:Liver / Q000032:analysis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000031:analogs & derivatives* / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D003497:Cyclic N-Oxides; C024270:nicotine 1-N-oxide; D009538:Nicotine