Trans-3’-hydroxycotinine

Quantitative aspects of the pattern of nicotine metabolism have been elucidated fairly well in people (Fig. 4). Approximately 90% of a systemic dose of nicotine can be accounted for as nicotine and metabolites in urine (Benowitz et al. 1994). Based on studies with simultaneous infusion of labeled nicotine and cotinine, it has been determined that 70-80% of nicotine is converted to cotinine (Benowitz and Jacob 1994). About 4-7% of nicotine is excreted as nicotine N -oxide and 3-5% as nicotine glucuronide (Benowitz et al. 1994 Byrd et al. 1992). Cotinine is excreted unchanged in urine to a small degree (10-15% of the nicotine and metabolites in urine). The remainder is converted to metabolites, primarily fra i -3 -hydroxycotinine (33 0%), cotinine glucuronide (12-17%), and trans-3 -hydroxycotinine glucuronide (7-9%). 

Byrd GD, Chang KM, Greene JM, deBethizy JD (1992) Evidence for urinary excretion of glu-curonide conjugates of nicotine, cotinine, and trans-3 -hydroxycotinine in smokers. Drug Metab Dispos 20(2) 192-197... 

Jacob P, 3rd, Benowitz NL (1991) Oxidative metabolism of nicotine in vivo. In F, Adlkofer, K, Thurau (eds) Effects of nicotine on biological systems, Birkhauser Verlag, Basel, pp 35 4 Jacob P, 3rd, Shulgin AT, Benowitz NL (1990) Synthesis of (3 R, 5 S)-trans-3 -hydroxycotinine, a major metabolite of nicotine. Metabolic formation of 3 -hydroxycotinine in humans is highly stereoselective, J Med Chem 33(7) 1888-1891... 

Neurath GB (1994) Aspects of the oxidative metabolism of nicotine. Clin Investig 72(3) 190-195 Neurath GB, Dunger M, Orth D, Pein FG (1987) Trans-3 -hydroxycotinine as a main metabolite in urine of smokers. Int Arch Occup Environ Health 59(2) 199-201 Neurath GB, Orth D, Pein FG (1991) Detection of nomicotine in human urine after infusion of nicotine. In Adlkofer F, Thurau K (eds) Effects of nicotine on biological systems. Birkhauser Verlag, Basel, pp 45 9... 

Yamanaka H, Nakajima M, Katoh M, Kanoh A, Tamura O, Ishibashi H, Yokoi T (2005a) Trans-3 -hydroxycotinine O- and N-glucuronidations in human liver microsomes. Drug Metab Dispos 33 23-30... 

Dobrinas M, Choong E, NoetzU M, Comuz J, Ansermot N, Eap CB. Quantification of nicotine, cotinine, trans-3 -hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC—tandem mass-spectrometry procedure for a clinical study on smoking cessation. J Chromatogr B Anal Tech Biomed Life Sci 2011 879 3574-82. 

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