Determination of the nicotine metabolite trans-3'-hydroxycotinine in urine of smokers using gas chromatography with nitrogen-selective detection or selected ion monitoring.
A gas chromatographic method for the determination of the nicotine metabolite trans-3'-hydroxycotinine is described. The method involves conversion of the metabolite to the tert.-butyldimethylsilyl derivative, chromatography on a fused-silica capillary column, and determination using nitrogen-phosphorus detection or electron ionization mass spectrometry with selected ion monitoring. A structural analogue, trans-3-hydroxy-1-methyl-5-(2-pyridyl)pyrrolidin-2-one (trans-3'-hydroxy-ortho-cotinine), was used as an internal standard. Using selected ion monitoring, good precision and accuracy were obtained for determination of trans-3'-hydroxycotinine in urine over the concentration range 10-10,000 ng/ml. There was a good correlation between concentrations determined by selected ion monitoring and by nitrogen-phosphorus detection in urine of smokers, although low concentrations determined using nitrogen-phosphorus detection tended to be somewhat higher, suggesting some interference from urinary constituents. Concentrations and 24-h excretion of trans-3'-hydroxycotinine in the urine of 22 cigarette smokers are reported and compared to concentrations and excretion of nicotine, cotinine, nicotine 1'-N-oxide, nornicotine, and cotinine N-oxide.
Jacob
P
P
Clinical Pharmacology Unit, San Francisco General Hospital, CA 94110.
Shulgin
A T
AT
Yu
L
L
Benowitz
N L
NL
D002849:Chromatography, Gas / Q000379:methods*; D003367:Cotinine / Q000031:analogs & derivatives* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007477:Ions; D009584:Nitrogen; D015203:Reproducibility of Results; D012907:Smoking / Q000652:urine*
D007477:Ions; C001381:hydroxycotinine; D003367:Cotinine; D009584:Nitrogen