Cotinine, formation

Precursors and Formation. Tobaccos used for commercial products in the U.S.A, contain between 0,5 and 2,7% alkaloids. Nicotine constitutes 85-95% of the total alkaloids (14,26,27). Important minor alkaloids are nornicotine, anatabine, anabasine, cotinine and N -formylnornicotine (Figure 6), Several of these alkaloids are secondary and tertiary amines and, as such, amenable to N-nitrosation. The N-nitrosated alkaloids identified to date in tobacco and tobacco smoke include N -nitrosonornico-tine (NNN), 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) and N -nitrosoanatabine (NAT Figure 7). In model experiments, nitrosation of nicotine also yielded 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA 28). 

Several compounds are inhibitors of CYP2A6-mediated nicotme metabolism m vitro, mcludmg methoxsalen (8-methoxypsoralen), tranylcypromine, tryptamine and coumarin (Le Gal et al. 2003 MacDougall et al. 2003 Nakajima et al. 1996 Zhang et al. 2001). Raloxifene is a potent inhibitor of aldehyde oxidase and it has been shown to inhibit the formation of cotinine from nicotme-A -iminium ion in human liver cytosol (Obach 2004). 

The major human urinary metabolites of nicotine are cotinine, nicotine A -oxide, and fra s-3 -hydroxycotinine (113). CYP2A6 appears to be the major enzyme responsible for formation of an iminium ion that is the first step in the C-5 oxidation of nicotine to cotinine and also the subsequent... 

GRAPEFRUIT JUICE NICOTINE Significant t renal clearance of nicotine Grapefruit juice inhibits the formation of cotinine from nicotine, t renal clearance of cotinine and 1 plasma concentrations of cotinine by 15% Be aware in patients using varying forms of nicotine replacement therapy for stopping smoking... 

Principles and characteristics of lateral flow strip assays are reviewed. Recent technology developments permit the use of inexpensive electronic readers for interrogating lateral flow strip test results, thus avoiding the inevitable variation and subjectivity of visual inspection to assess the capture of reporter-labeled analyte on test lines of the strip. Protocols for developing lateral flow assays are described, including two specific case studies for assaying cotinine (a small-molecule metabolite of nicotine) in a competitive format, and assaying HIV antibodies in a sandwich-type assay format. 

Djordjevic et al. (1012) identified 4-(A-methylnitrosa-mino)-4-(3-pyridinyl)-l-butanoic acid (Ao-NNAC) in tobacco and in MSS. This acid was found only in the MSS from cigarettes containing tobacco spiked (2 mg/cigarette) with cotinine. From the results of in vitro nitrosation studies with radiolabeled cotinine and nicotine, Djordjevic et al. (995) proposed that the formation of 4-(A-methylnitrosamino)-4-(3-pyridinyl)-l-butanoic acid (Ao-NNAC) in tobacco proceeds via cotinine and its hydrolysis product 4-methyl-4-(3-pyridinyl)-l-butanoic acid rather than via nicotine. 

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