Urine nicotine

Kandel DB, Hu MC, Schaffran C, Udry JR, Benowitz NL (2007) Urine nicotine metabolites and smoking behavior in a multiracial/multiethnic national sample of young adults. Am J Epidemiol... 

Quantification. High Pressure Liquid Chromatography. In plasma or urine nicotinic acid and nicotinuric acid, sensitivity 500 ng/ml, UV detection—N. Hengen et al., Clin. Chem., 1978,... 

None or minimal "direct injection" Ease, speed, cost, potential for automation Rarely feasible, requires relatively clean matrix (i.e., urine) and analyte that requires no preconcentration, may still require filtration or centrifugation to clarify sample Urine nicotine and metabolites by LC-MS/MS [1]... 

For more specific analysis, chromatographic methods have been developed. Using reverse-phase columns and uv detection, hplc methods have been appHed to the analysis of nicotinic acid and nicotinamide in biological fluids such as blood and urine and in foods such as coffee and meat. Derivatization techniques have also been employed to improve sensitivity (55). For example, the reaction of nicotinic amide with DCCI (AT-dicyclohexyl-0-methoxycoumarin-4-yl)methyl isourea to yield the fluorescent coumarin ester has been reported (56). After separation on a reversed-phase column, detection limits of 10 pmol for nicotinic acid have been reported (57). 

Trigonelline appears to exert no marked physiological action. Ackermann first observed that nicotinic acid administered to dogs appears in the urine as trigonelline. 

The range of nicotinic acid activity in blood, for a group of 28 normal subjects is 3.9-9.6 qg/ml. Only a fraction of less than 1% (0.016-0.05 pg/ml) of this quantity was present in serum. The range in urine was 1.16-1.54 pg/ml. Ninety-seven to 101% of added combinations of nicotinic acid and nicotinamide was recovered when added to blood and urine. In blood, appreciable nicotinic activity is observed only after... 

The biosynthesis and metabolism of nicotinic acid in disease has received little attention metabolic studies deal mainly with normal animals and man (01, R5). After a tryptophan load dose, the main catabolites in the urine are nicotinuric acid, N1-methylnicotinamide, nicotinamide, quinolinic acid, kynurenine, 6-pyridone, anthranilic acid, and 3-hydroxyanthranilic acid. These excretory products were estimated... 

We have developed a direct assay for vitamin Be in blood, serum, urine, cerebrospinal fluid, and tissue, based on the ciliate, Tetrahymena pyriformvs. The techniques are essentially those described for nicotinic acid (see Section 4.1), except that vitamin Be is omitted from the basal medium both nicotinic acid and its amide are added each at 0.1 mg/100 ml of basal medium. The method for blood, serum, urine, cerebrospinal fluid, and tissues is given below. 

Tuomi T, Johnsson T, Reijula K. 1999. Analysis of nicotine, 3-hydroxycotinine, cotenine, and caffeine in urine of passive smokers by HPLC-tandem mass spectrometry. Clin Chem 45 2164. 

Nicotine glucmonidation results in an N-quatemary glucmonide in humans (Benowitz et al. 1994). This reaction is catalyzed by uridine diphosphate-glucuronosyltransferase (UGT) enzyme(s) producing (5)-nicotine-N-P-glucmonide. About 3-5% of nicotine is converted to nicotine glucuronide and excreted in urine in humans. 

Although on average about 70-80% of nicotine is metabolized via the cotinine pathway in humans, only 10-15% of nicotine absorbed by smokers appears in the urine as unchanged cotinine (Benowitz et al. 1994). Six primary metabolites of cotinine have been reported in humans 3 -hydroxycotinine (McKennis et al. 1963 Neurath et al. 1987), 5 -hydroxycotinine (also called allohydroxycotinine) (Neurath 1994), which exists in tautomeric equilibrium with the open chain derivative... 

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%). 

Neonates have diminished nicotine metabolism, as demonstrated by a nicotine half-life of three to four times longer in newborns exposed to tobacco smoke than in adnlts (Dempsey et al. 2000). Cotinine half-life is reported to be similar in neonates, older children, and adults in two studies (Dempsey et al. 2000 Leong et al. 1998). Other studies found that the half-life of urine cotinine was about three times longer in children less than one year old than to the cotinine half-life in adults (Collier et al. 1994). Urine cotinine half-life can be influenced by variations in urine volume and excretion of creatinine. The study by Dempsey et al. was the only one in which the half-life of cotinine was calculated based on both the blood and urine cotinine concentrations (Dempsey et al. 2000). In that study, both the blood and urine half-lives were similar to adult values, supporting the notion that neonates have the same cotinine half-life as older children and adults. 

In vitro stndies have shown that there are distinct transport systems for both baso-lateral and apical uptake of nicotine (Takami et al. 1998). Nicotine has been shown to be actively transported by kidney cells, most likely by the organic ion transporter OCT2 (Zevin et al. 1998 Urakami et al. 1998). Cimetidine decreases renal clearance of nicotine by 47% in nonsmoking volunteers (Bendayan et al. 1990). This is consistent with the inhibition of basolateral uptake by cimetidine detected in vitro. Mecamylamine reduces renal clearance of nicotine in smokers dosed with intra-venons nicotine when urine is alkalinized, but not when nrine is acidified (Zevin et al. 2000). 

Renal clearance of cotinine is much less than the glomerular filtration rate (Benowitz et al. 2008b). Since cotinine is not appreciably protein bound, this indicates extensive tnbnlar reabsorption. Renal clearance of cotinine can be enhanced by np to 50% with extreme urinary acidification. Cotinine excretion is less influenced by urinary pH than nicotine becanse it is less basic and, therefore, is primarily in the unionized form within the physiological pH range. As is the case for nicotine, the rate of excretion of cotinine is influenced by urinary flow rate. Renal excretion of cotinine is a minor route of elimination, averaging about 12% of total clearance. In contrast, 100% of nicotine Ai -oxide and 63% of 3 -hydroxycotinine are excreted unchanged in the urine (Benowitz and Jacob 2001 Park et al. 1993). 

Nicotine Nicotine Blood, urine, saliva, hair 1-2 h Yes Nicotine replacement products... 

The primary alkaloid in tobacco is nicotine, but tobacco also contains small amounts of minor alkaloids such as anabasine, anatabine, myosmine, and others. The minor alkaloids are absorbed systemically and can be measured in the urine of smokers and users of smokeless tobacco (Jacob et al. 1999). The measurement of minor alkaloids is a way to quantitate tobacco use when a person is also taking in pure nicotine from a nicotine medication or a nontobacco nicotine delivery system. This method has been used to assess tobacco abstinence in clinical trials of smoking cessation with treatment by nicotine medications (Jacob et al. 2002). 

Al-Delaimy WK, Crane J, Woodward A (2002) Is the hair nicotine level a more accurate biomarker of environmental tobacco smoke exposure than urine cotinine J Epidemiol Community Health 56(1) 66-71... 

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... 

Stepanov I, Hecht SS, Lindgren B, Jacob P 3rd, Wilson M, Benowitz ML (2007) Relationship of human toenail nicotine, cotinine, and 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanol to levels of these biomarkers in plasma and urine. Cancer Epidemiol Biomarkers Prev 16(7) 1382-1386 Swan GE, Benowitz NL, Lessov CN, Jacob P, 3rd, Tyndale RE, Wilhelmsen K (2005) Nicotine metabolism the impact of CYP2A6 on estimates of additive genetic influence. Pharmacogenet Genomics 15(2) 115-125... 

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