Nicotine is the major alkaloid present in tobacco and the most frequently determined compound as a biomarker of tobacco exposure in both smokers and non-smokers exposed to environmental tobacco smoke. Current knowledge on the human metabolism and disposition kinetics of nicotine is reviewed, together with methods for the determination of nicotine and various metabolites in different human biological fluids and matrices. Only short-term biomarkers of nicotine exposure exist and long-term biomarkers of exposure such as the incorporation of nicotine and cotinine into human hair, toenails and deciduous teeth require further investigation. Determination of ‘nicotine boost’, the difference in blood nicotine concentrations that occur after smoking a single cigarette, provides an experimental indication of individual smoking behaviour, but is unsuitable for population studies. The determination of nicotine plus multiple phase I and phase II metabolites in 24-hour urine, often expressed as ‘nicotine equivalents’, provides the most accurate way to determine exposure to nicotine in smokers; however, few laboratories are equipped to perform the complex analysis required for this purpose. Nicotine equivalents can be used to estimate the uptake of nicotine from a cigarette in both individuals and in population studies. Despite recent advancements in analytical methodology and the possibility of determining multiple nicotine metabolites in various biological fluids, determination of cotinine, the major metabolite of nicotine, is likely to remain the most commonly used approach to assess exposure to tobacco smoke in both smokers and non-smokers. Representative data for cotinine in blood, saliva and urine of smokers and non-smokers are presented.
1. Jarvis, M.J., H. Tunstall-Pedoe, C. Feyerabend, C. Vesey, and Y. Saloojee: Comparison of tests used to distinguish smokers from nonsmokers; Am. J. Public Health 77 (1987) 1435-1438.
2. Patrick, D.L., A. Cheadle, D.C. Thompson, P. Diehr, T. Koepsell, and S. Kinne: The validity of self-reported smoking: a review and meta-analysis; Am. J. Resp. Crit. Care Med. 84 (1994) 1086-1093.
3. Boyd, N.R., R.A. Windsor, L.L. Perkins, and J.B. Lowe: Quality of measurement of smoking status by self-report and saliva cotinine among pregnant women; Matern. Child Health J. 2 (1998) 77-83.
4. Lindqvist, R., L. Lendahls, Ö. Tollbom, H. Åberg, and A. Håkansson: Smoking during pregnancy: comparison of self-reports and cotinine levels in 496 women; Acta Obstet. Gynecol. Scand. 81 (2002) 240-244.
5. Lee, P.N. and B.A. Forey: Misclassification of smoking habits as determined by cotinine or by repeated self-report - a summary of evidence from 42 studies; J. Smoking-Related Dis. 6 (1995) 109-129.
6. Scherer, G. and E. Richter: Biomonitoring exposure to environmental tobacco smoke (ETS): a critical reappraisal; Human Exp. Toxicol. 16 (1997) 449-459.
7. Haley, N.J., CM. Axelrod, and K.A. Tilton: Validation of self-reported smoking behavior: biochemical analysis of cotinine and thiocyanate; Am. J. Public Health 73 (1983) 1204-1207.
8. Van Vunakis, H., D.P. Tashkin, B. Rigas, M. Simmons, H.B Gjika, and V.A. Clark: Relative sensitivity and specificity of salivary and serum cotinine in identifying tobacco-smoking status of self-reported nonsmokers and smokers of tobacco and/or marijuana; Arch. Environ. Health 44 (1989) 53-58.
9. Tunstall-Pedoe, H., M. Woodward, and C.A. Brown: Tea drinking, passive smoking, smoking deception and serum cotinine in the Scottish Heart Health Study; J. Clin. Epidemiol. 44 (1991) 1411–1414.
10. Murray, R.P., J.E. Connett, J.A. Istvan, M.A. Nides, and S. Rempel-Rossum: Relations of cotinine and carbon monoxide to self-reported smoking in a cohort of smokers and ex-smokers followed over 5 years; Nicotine Tob. Res. 4 (2002) 287–294.
11. Scherer, G.: Smoking behaviour and compensation: a review of the literature; Psychopharmacology (Berl.) 145 (1999) 1–20.
12. Haley, N.J., S.G. Colosimo, C.M. Axelrad, R. Harris, and D.W. Sepkovic: Biochemical validation of self-reported exposure to environmental tobacco smoke; Environ. Res. 49 (1989) 127–135.
13. Benowitz, N.L.: Cotinine as a biomarker of environmental tobacco smoke exposure; Epidemiol. Rev. 18 (1996) 188–204.
14. DeLorenze, G.N., M. Kharrazi, F.L. Kaufman, B. Eskenazim, and J.F. Bernert: Exposure to environ-mental tobacco smoke in pregnant women: The association between self-report and serum cotinine; Environ. Res. 90 (2002) 21–32.
15. Jarvis, M.J.: Trends in sales weighted tar, nicotine and carbon monoxide yields of UK cigarettes; Thorax 56 (2001) 960–963.
16. Wortley, P.M., R.S. Carabello, L.L. Pederson, and T.F. Pechacek: Exposure to secondhand smoke in the workplace: Serum cotinine by occupation; J. Occup. Environ. Med. 44 (2002) 503–509.
17. Seccareccia, F., P. Zuccaro, R. Pacifici, P. Meli, F. Pannozzo, K.M. Freeman, A. Santaquilani, S. Giam-paoli: Serum cotinine as a marker of environmental tobacco smoke exposure in epidemiological studies: The experience of the MATISS project; Eur. J. Epide-miol. 18 (2003) 487–492.
18. Palmer, K.J., M.M. Buckley, and D. Faulds: Transdermal nicotine: A review of its pharmacodyna-mic and pharmacokinetic properties and therapeutic efficacy as an aid to smoking cessation. Drugs 44 (1992) 498–529.
19. Sutherland, G., M.A.H. Russell, J. Stapleton, C. Feyer-abend, and O. Ferno: Nasal nicotine spray: A rapid nicotine delivery system; Psychopharmacology (Berl.) 108 (1992) 512–518.
20. Guthrie, S.K., J.-K. Zubieta, L. Ohl, L. Ni, R.A. Koeppe, S. Minoshima, and E.F. Domino: Arterial/venous plasma nicotine concentrations following nicotine nasal spray; Eur. J. Clin. Pharmacol. 55 (1999) 639–643.
21. Ji, A.J. Jr., G.M. Lawson, R. Anderson, L.C. Dale, I.T. Croghan, and R.D. Hurt: A new gas chromatography-mass spectrometry method for simultaneous deter-mination of total and free trans-3’-hydroxycotinine and cotinine in the urine of subjects receiving transdermal nicotine; Clin. Chem. 45 (1999) 85–91.
22. Hurt, R.D., G.A. Croghan, S.D. Beede, T.D. Wolter, I.T. Crogan, and C.A. Patten: Nicotine patch therapy in 101 adolescent smokers; Arch. Pediatr. Adolesc. Med. 154 (2000) 31–37.
23. Schneider, N.G., R.E. Olmstead, M.A. Franzon, and E. Lunell: The nicotine inhaler. Clinical pharmacokinetics and comparison with other nicotine treatments; Clin. Pharmacokinet. 40 (2001) 661–684.
24. Miwa, K., Y. Miyagi, H. Asanoi, M. Fujita, and S. Sasayama: Augmentation of smoking cessation education by urinary cotinine measurements; Jpn. Circ. J. 57 (1993) 775–780.
25. Trudeau, D.L., C. Isenhard, and D. Silversmith: Efficacy of smoking cessation strategies in a treatment program; J. Addict. Dis. 14 (1995) 109–116.
26. Secker-Walker, R.H., P.M. Vacek, B.S. Flynn, and P.B. Mead: Exhaled carbon monoxide and urinary cotinine as measures of smoking in pregnancy; Addict. Behav. 22 (1997) 671–684.
27. Davis, R.A., M.F. Stiles, J.D. deBethizy, and J.H. Reynolds: Dietary nicotine: a source of urinary cotinine; Food Chem. Toxicol. 29 (1991) 821–827.
28. Siegmund, B., E. Leitner, and W. Pfannhauser: Determination of nicotine content of various edible nightshades (Solanaceae) and their products and estimation of the associated dietary nicotine intake; J. Agric. Food Chem. 47 (1999) 3113–3120.
29. Armstrong, D.W., X. Wang and N. Ercal: Enantiometric composition of nicotine in smokeless tobacco, medicinal products and commercial reagents; Chirality 10 (1998) 587–591.
30. Pool, W.F., C.S. Godin, and P.A. Crooks: Nicotine racemization during tobacco smoking; The Toxicologist 5 (1985) 232.
31. Armitage, A.K. and D.M. Turner: Absorption of nicotine in cigarette and cigar smoke through the oral mucosa; Nature 226 (1970) 1231–1232.
32. Beckett, A.H., J.W. Gorrod, and P. Jenner: A possible relationship between pKa1 and lipid solubility and the amounts excreted in urine of some tobacco alkaloids given to man; J. Pharm. Pharmac. 24 (1972) 115–120.
33. Armitage, A., C. Dollery, T. Houseman, E. Kohner, P.J. Lewis, and D. Turner: Absorption of nicotine from small cigars; Clin. Pharmacol. Ther. 23 (1978) 143–151.
34. Armitage, A.K., M. Dixon, B.E. Frost, D.C. Mariner, and N.M. Sinclair: The effect of tobacco blend additives on the retention of nicotine and solanesol in the human respiratory tract and on subsequent plasma nicotine concentrations during cigarette smoking; Chem. Res. Toxicol. 17 (2004) 537–544.
35. Wald, N.J., M. Idle, J. Boreham, A. Bailey, and H. Van Vunakis: Serum cotinine levels in pipe smokers: Evidence against nicotine as a cause of coronary heart disease; Lancet 2 (1981) 775–777.
36. Gori, G.B., N.L. Benowitz, and C.J. Lynch: Mouth verses deep airways absorption of nicotine in cigarette smokers. Pharmacol; Biochem. Behav. 25 (1986) 1181–1184.
37. Rieben, F.W.: Smoking behaviour and increase in nicotine and carboxyhaemoglobin in venous blood; Clin. Invest. 70 (1992) 335–342.
38. Benowitz, N.L.: Pharmacologic aspects of cigarette smoking and nicotine addiction; N. Engl. J. Med. 319 (1988) 1318–1330.
39. Armitage, A.K., C.T. Dollery, C.F. George, T.H. Houseman, P.J. Lewis, and D.M. Turner: Absorption and metabolism of nicotine from cigarettes; Br. Med. J. 4 (1975) 313–316.
40. Henningfield, J.E., E.D. London, and N.L. Benowitz: Arterial-venous differences in plasma concentrations of nicotine after cigarette smoking; JAMA 263 (1990) 2049–2050.
41. Lunell, E., L. Molander, K. Ekberg, and J. Wahren: Site of nicotine absorption from a vapour inhaler – comparison with cigarette smoking; Eur. J. Pharmacol. 55 (2000) 737–741.
42. Herning, R.I., R.T. Jones, N.L. Benowitz, and A.H. Mines: How a cigarette is smoked determines nicotine blood levels; Clin. Pharmacol. Ther. 33 (1983) 84–90.
43. Adlkofer, F., G. Scherer, A. Biber, W.-D. Heller, P.N. Lee, and H. Schievelbein: Consistency of nicotine intake in smokers of cigarettes with varying nicotine yields; in: Nicotine, Smoking and the Low Tar Programme, edited by N. Wald and P. Froggart; Oxford University Press, Oxford, 1989, pp. 116–130.
44. Byrd, G.D., J.H. Robinson, W.S. Caldwell, and J.D. deBethizy: Comparison of measured and FTC-predicted nicotine uptake in smokers; Psychopharmacology 122 (1995) 95–103.
45. Benowitz, N.L., F. Kuyt, and P. Jacob III.: Circadian blood nicotine concentrations during cigarette smoking; Clin. Pharmacol. Ther. 32 (1982) 758–764.
46. Russell, M.A.H., C. Wilson, U.A. Patel, C. Feyerabend, and P.V. Cole: Plasma nicotine levels after smoking cigarettes with high, medium and low nicotine yields; Br. Med. J. 2 (1975) 414–416.
47. Russell, M.A.H., M. Jarvis, R. Iyer, and C. Feyerabend: Relationship of nicotine yield of cigarettes to blood nicotine concentration in smokers; Br. Med. J. (1980) 972–976.
48. Benowitz, N.L., S.M. Hall, R.L. Herning, P. Jacob, III., R.T. Jones, and A.-L. Osman: Smokers of low-yield cigarettes do not consume less nicotine; N. Engl. J. Med. 309 (1983) 139–142.
49. Ebert, R.V., K.E. McNabb, K.T. McCuskar, and S.L. Snow: Amount of nicotine and carbon monoxide inhaled by smokers of low-tar, low-nicotine cigarettes; JAMA 250 (1983) 2840–2842.
50. Gori, G.B. and C.J. Lynch: Smoker intake from cigarettes in the 1-mg Federal Trade Commission tar class; Regul. Toxicol. Pharmacol. 3 (1983) 110–120.
51. Gori, G.B. and C.J. Lynch: Analytical cigarette yields as predictors of smoke bioavailability; Regul. Toxicol. Pharmacol. 5 (1985) 314–326.
52. Benowitz, N.L. and P. Jacob III.: Daily intake of nicotine during cigarette smoking; Clin. Pharmacol. Ther. 35 (1984) 499–504.
53. Feyerabend, C., R.M.J. Ings, and M.A.H. Russell: Nicotine pharmacokinetics and its application to intake from smoking; Br. J. clin. Pharmac. 19 (1985) 239–247.
54. Bridges, R.B., J.W. Humble, J.A. Turbek, and S.R. Rehm: Smoking history, cigarette yield and smoking behavior as determinants of smoke exposure; Eur. J. Respi. Dis. 69 (Suppl. 146) (1986) 129–137.
55. Bridges, R.B., J.G. Combs, J.W. Humble, J.A. Turbek, S.R. Rehm, and N.J. Haley: Population characteristics and cigarette yield as determinants of smoke exposure; Pharmacol. Biochem. Behav. 37 (1990) 17–28.
56. Zacny, J.P. and M.L. Stitzer: Cigarette brand-switching: effects on smoke exposure and smoking behavior; J. Pharmacol. Expt. Ther. 246 (1988) 619–627.
57. Kolonen, S.A. and E.V.J. Puhakainen: Assessment of the automated colorimetric and the high-performance liquid chromatographic methods for nicotine intake by urine samples of smokers’ smoking low- and medium-yield cigarettes; Clin. Chim. Acta 196 (1991) 159–166.
58. Bruckert, E., N. Jacob, L. Lamaire, J. Truffert, F. Percheron, and J.L. de Gennes: Relationship between smoking status and serum lipids in a hyperlipidemic population and analysis of possible confounding factors; Clin. Chem. 38 (1992) 1698–1705.
59. Woodward, M. and H. Tunstall-Pedoe: Self-titration of nicotine: evidence from the Scottish Heart Health Study; Addiction 88 (1993) 821–830.
60. Coultas, D.B., C.A. Stidley, and J.M. Samet: Cigarette yields of tar and nicotine and markers of exposure to tobacco smoke; Am. Rev. Respir. Dis. 148 (1993) 435–440.
61. Hee, J., F. Callais, I. Momas, A.M. Laurent, S. Min, P. Molinier, M. Chastagnier, J.R. Claude, and B. Festy: Smokers’ behavior and exposure according to cigarette yield and smoking experience; Pharmacol. Biochem. Behav. 52 (1995) 195–203.
62. Andersson, G., E.K. Vala, and M. Curvall: The influence of cigarette consumption and smoking machine yields of tar and nicotine on the nicotine uptake and oral mucosal lesions in smokers; J. Oral Pathol. Med. 26 (1997) 117–123.
63. Byrd, G.D., R.A. Davies, W.S. Caldwell, J.H. Robinson, and J.D. deBethizy: A further study of FTC yield and nicotine absorption in smokers. Psycho-pharmacology 139 (1998) 291–229.
64. Jarvis, M.J., R. Boreham, P. Primatesta, C. Feyerabend, and A. Bryant: Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: Evidence from a representative population survey; J. Natl. Cancer Inst. 93 (2001) 134–138.
65. Ueda, K., I. Kawachi, M. Nakmura, H. Nogami, N. Shirokawa, S. Masui, A. Okayama, and A. Oshima: Cigarette nicotine yields and nicotine intake among Japanese male smokers; Tobacco Control 11 (2002) 55–60.
66. Nakazawa, A., M. Shigeta, and K. Ozasa: Smoking cigarettes of low nicotine yield does not reduce nicotine intake as expected: A study of nicotine dependency in Japanese males; BMC Public Health 4 (2004) 28.
67. Federal Trade Commission: Cigarettes. Testing for tar and nicotine content – statements of considerations; Fed. Regist. 32 (1967) 11178.
68. Sato, H. and S. Araki: Yields and daily consumption of cigarettes in Japan in 1969–1966; J. Epidemiol. 10 (2000) 7–15.
69. National Cancer Institute: Risks associated with cigarette smoking with low machine-measured yields of tar and nicotine. Smoking and Tobacco Control Monograph No. 13. Bethesda, MD: U.S. Department of Health and Human Services, National Institute of Health, National Cancer Institute; NIH Publ. No. 02-5074, 2001.
70. Benowitz, N.L., P. Jacob, III., C. Denaro, and R. Jenkins: Stable isotope studies of nicotine kinetics and bioavailability; Clin. Pharmacol. Ther. 49 (1991) 270–277.
71. Benowitz, N.L. and P. Jacob, III.: Metabolism of nicotine to cotinine studied by a dual stable isotope method; Clin. Pharmacol. Ther. 56 (1994) 483–493.
72. Pérez-Stable, E.J., B. Herrera, P. Jacob III., and N.L. Benowitz: Nicotine metabolism and intake in black and white smokers; JAMA 280 (1998) 152–156.
73. Benowitz, N.L., E.J. Pérez-Stable, B. Herrera, and P. Jacob III.: Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans; J. Natl. Cancer Inst. 94 (2002) 108–115.
74. Byrd, G.D., K.-M. Chang, J.M. Greene, and J.D. deBethizy: Evidence for urinary excretion of glucu-ronide conjugates of nicotine, cotinine and trans-3’-hydroxycotinine in smokers; Drug Metab. Dispos. 20 (1992) 192–197.
75. Curvall, M., E. Kazemi-Vala, and G. Englund: Conjugation pathways in nicotine metabolism; in: Effects of Nicotine on Biological Systems, edited by F. Adlkofer and K. Thurau, Birkhäuser Verlag, Basel, 1991, pp. 69–75.
76. Seaton, M.J., E.S. Vesell, H. Luo, and E.M. Hawes: Identification of radiolabeled metabolites of nicotine in rat bile. Synthesis of S-(–)-nicotine N-glucuronide and direct separation of nicotine-derived conjugates using high-performance liquid chromatography; J. Chroma-togr. 621 (1993) 49–53.
77. Caldwell, W.S., J.M. Greene, G.D. Byrd, K.M. Chang, M.S. Uhrig, J.D. deBethizy, P.A. Crooks, B.S. Bhatti, and R.M. Riggs: Characterization of the glucuronide conjugate of cotinine: A previously unidentified major metabolite of nicotine in smokers’ urine; Chem. Res. Toxicol. 5 (1992) 280–285.
78. Schepers, G., D. Demetriou, K. Rustemeier, P. Voncken, and B. Diehl: Nicotine phase 2 metabolites in human urine – structure of metabolically formed trans-3’-hydroxycotinine glucuronide; Med. Sci. Res. 20 (1992) 863–865.
79. Gorrod, J.W. and G. Schepers: Biotransformation of nicotine in mammalian systems; in: Analytical Determination of Nicotine and Related Compounds and their Metabolites, edited by J.W. Gorrod and P. Jacob, III., Elsevier, Amsterdam, 1999, pp. 45–67.
80. De Schepper, P.J., A. Van Heecken, P. Daenens, and J.M. Van Rossum: Kinetics of cotinine after oral and intravenous administration; Eur. J. Clin. Pharmacol. 31 (1987) 583–588.
81. Scherer, G., L. Jarczyk, W.-D. Heller, A. Biber, G.B. Neurath, and F. Adlkofer: Pharmacokinetics of nicotine, cotinine and 3’-hydroxycotinine in cigarette smokers. Klin. Wochenschr. 66 (Suppl. XI)(1988) 5–11.
82. Kyerematen, G.A., M.L. Morgan, B. Chattopadhyay, J.D. deBethizy, and E.S. Vesell: Disposition of nicotine and eight metabolites in smokers and nonsmokers: Identification in smokers of two metabolites that are longer lived than cotinine; Clin. Pharmacol. Ther. 48 (1990) 641–651.
83. Curvall, M., E. Kazemi-Vala, C.R. Enzell, and J. Wahren: Simulation and evaluation of nicotine intake during passive smoking: Cotinine measurements in body fluids of nonsmokers given intraveneous infusions of nicotine; Clin. Pharmacol. Ther. 47 (1990) 42–49.
84. Curvall, M., C.-E. Elwin, E. Kazemi-Vala, C. Warholm, and C.R. Enzell: The pharmacokinetics of cotinine in plasma and saliva from non-smoking healthy volunteers; Eur. J. Clin. Pharmacol. 38 (1990) 281–287.
85. Kyerematen, G.A. and E.S. Vesell: Metabolism of nicotine; Drug Metab. Rev. 23 (1991) 3–41.
86. Benowitz, N.L. and P. Jacob, III.: Effects of cigarette smoking and carbon monoxide on nicotine and cotinine metabolism; Clin. Pharmacol. Ther. 67 (2000) 653–659.
87. Benowitz, N.L. and P. Jacob, III.: Trans-3’-hydroxyco-tinine: disposition kinetics, effects and plasma levels during cigarette smoking; J. Clin. Pharmacol. 51 (2001) 53–59.
88. Benowitz, N.L., E.J. Perez-Stable, I. Fong, G. Modin, B. Herrera, and P. Jacob, III.: Ethnic differences in N-glucuronidation of nicotine and cotinine; J. Pharmacol. Exp. Ther. 291 (1999) 1196–1203.
89. Zevin, S., P. Jacob, III., P. Geppetti, and N.L. Benowitz: Clinical pharmacology of oral cotinine; Drug Alcohol Depend. 60 (2000) 13–18.
90. Benowitz, N.L. and P. Jacob, III.: Nicotine and cotinine elimination pharmacokinetics in smokers and non-smokers; Clin. Pharmacol. Ther. 53 (1993) 316–323.
91. Langmann, P., A. Bienert, M. Zilly, T. Väth, E. Richter, and H. Klinker: Influence of smoking on cotinine and caffeine plasma levels in patients with alcoholic liver cirrhosis; Eur. J. Med. Res. 5 (2000) 217–221.
92. Molander, L., A. Hansson, E. Lunell, L. Alainentalo, M. Hoffmann, and R. Larsson: Pharmacokinetics of nicotine in kidney failure; Clin. Pharmacol. Ther. 68 (2000) 250–260.
93. Benowitz, N.L., P. Jacob, III., I. Fong, and S. Gupta: Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine; J. Pharmacol. Exp. Ther. 268 (1994) 296–303.
94. Molander, L., A. Hansson, and E. Lunell: Pharmacokinetics of nicotine in healthy elderly people; Clin. Pharmacol. Ther. 69 (2001) 57–65.
95. Dempsey, D., P. Jacob, III., and N.L. Benowitz: Accelerated metabolism of nicotine and cotinine in pregnant smokers; J. Pharmacol. Expt. Ther. 301 (2002) 594–598.
96. Dempsey, D., P. Jacob, III., and N.L. Benowitz: Nicotine metabolism and elimination kinetics in newborns; Clin. Pharmacol. Ther. 67 (2000) 458–465.
97. Hecht, S.S., S.G. Carmella, and S.E. Murphy: Effects of watercress consumption on urinary metabolites of nicotine in smokers; Cancer Epidemiol. Biomarkers Prev. 8 (1999) 907–913.
98. Meger, M., I. Meger-Kossien, A. Schuler-Metz, D. Janket, and G. Scherer: Simultaneous determination of nicotine and eight metabolites in urine of smokers using liquid chromatography – tandem mass spectrometry; J. Chromatogr. B 778 (2002) 251–261.
99. Benowitz, N.L., B. Herrera, and P. Jacob, III.: Mentholated cigarette smoking inhibits nicotine metabolism; J. Pharmacol. Expt. Ther. 310 (2004) 1208–1215.
100. Flammang, A.M., H.V. Gelboin, T. Aoyama, F.J. Gonzales, and G.D. McCoy: Nicotine metabolism by cDNA-expressed human cytochrome P-450s; Biochem. Arch. 8 (1992) 1–8.
101. McCracken, N.W., S. Cholerton, and J.R. Idle: Cotinine formation by cDNA-expressed human cytochromes P450; Med. Sci. Res. 20 (1992) 877–878.
102. Nakajima, M., T. Yamamoto, K. Nunoya, T. Yokoi, K. Nagashima, K. Inoue, Y. Funae, N. Shimada, T. Kamataki, and Y. Kuroiwa: Role of human cytochrome P4502A6 in C-oxidation of nicotine; Drug Metab. Dispos. 24 (1996) 1212–1217.
103. Bao, Z., T. Su, X. Ding, and J.-Y. Hong: Metabolism of nicotine and cotinine by human cytochrome P450 2A13 (CYP2A13); 13th International Symposium on Micro-somes and Drug Oxidations, July 10–14 2000, Stressa, Italy, Abstract 137.
104. Messina, E.S., R.F. Tyndale, and E.M. Sellers: A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes; J. Pharmacol. Exp. Ther. 282 (1997) 1608–1614.
105. Yamazaki, H., K. Inoue, M. Hashimoto, and T. Shimada: Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes; Arch. Toxicol. 73 (1999) 65–70.
106. Nakajima, M., T. Yamamoto, K. Nunoya, T. Yokoi, K. Nagashima, K. Inoue, Y. Funae, N. Shimada, T. Kamataki, and Y. Kuroiwa: Characterization of CYP2A6 involved in 3’-hydroxylation of cotinine in human liver microsomes; J. Pharmacol. Exp. Ther. 277 (1996) 1010–1015.
107. Benowitz, N.L., P. Jacob, III., and E. Perez-Stable: CYP2D6 phenotype and the metabolism of nicotine and cotinine; Pharmacogenetics 6 (1996) 239–242.
108. Marez, D., M. Legrand, N. Sabbagh, J.-M. LoGuidice, C. Spire, J.-J. Lafitte, U.A. Meyer, and F. Broly: Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution; Pharmacogenetics 7 (1997) 193–202.
109. Lang, T., K. Klein, J. Fisher, A.K. Nüssler, P. Neuhaus, U. Hofmann, M. Eichelbaum, M. Schwab, and U.M. Zanger: Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver; Pharmacogenetics 11 (2001) 399–415.
110. Tricker, A.R.: Nicotine metabolism, human drug metabolism polymorphisms and smoking behaviour; Toxicology 183 (2003) 151–173.
111. Zhang, X., Y. Chen, Y. Liu, X. Ren, Q.Y. Zhang, M. Caggana, and X. Ding: Single nucleotide polymor-phisms of the human cyp2a13 gene: Evidence for a null allele; Drug Metab. Dispos. 30 (2003) 1081–1085.
112. Cashman, J.R., S.B. Park, Z.C. Yang, S.A. Wrighton, P. Jacob, III., and N.L. Benowitz: Metabolism of nicotine by human liver microsomes: Stereoselective formation of trans-nicotine N’-oxide; Chem. Res. Toxicol. 5 (1992) 639–646.
113. Kuehl, G. and S.E. Murphy: N-Glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltrans-ferases; Drug Metab. Dispos. 31 (2003) 1361–1368.
114. Benowitz, N.L. and P. Jacob, III.: Individual differences in nicotine kinetics and metabolism in humans; NIDA Res. Monogr. 173 (1997) 48–64.
115. Sellers, E.M.: Pharmacogenetics and ethnoracial differences in smoking; JAMA 280 (1998) 179–180.
116. Russell, M.A.H. and C. Feyerabend: Cigarette smoking: a dependence on high-nicotine boli; Drug Metab. Rev. 8 (1978) 29–57.
117. Benowitz, N.L., O.F. Pomerleau, C.S. Pomerleau, and P. Jacob, III.: Nicotine metabolite ratio as a predictor of cigarette consumption; Nicotine Tob. Res. 5 (2003) 621–624.
118. Davis, R.A. and M. Curvall: Determination of nicotine and its metabolites in biological fluids: in vivo studies; in: Analytical Determination of Nicotine and Related Compounds and their Metabolites, edited by J.W. Gorrod and P. Jacob, III., Elsevier, Amsterdam, 1999, pp. 583–644.
119. Smith, R.F., H.M. Mather, and G.A. Ellard: Assessment of simple colorimetric procedures to determine smoking status of diabetic subjects; Clin. Chem. 44 (1998) 275–280.
120. Langone, J.J., H.B. Gjika, and H. Van Vunakis: Use of immunoassay techniques for the determination of nicotine and its metabolites; in: Analytical Determination of Nicotine and Related Compounds and their Metabolites, edited by J.W. Gorrod and P. Jacob, III., Elsevier, Amsterdam, 1999, pp. 265–284.
121. Jacob, P., III and G.D. Byrd: Use of gas chromato-graphic and mass spectrometric techniques for the deter-mination of nicotine and its metabolites; in: Analytical Determination of Nicotine and Related Compounds and their Metabolites, edited by J.W. Gorrod and P. Jacob, III., Elsevier, Amsterdam, 1999, pp. 191–224.
122. Crooks, P.A. and G.D. Byrd: Use of high performance liquid chromatographic-mass spectrometric (LC-MS) techniques for the determination of nicotine and its metabolites; in: Analytical Determination of Nicotine and Related Compounds and their Metabolites, edited by J.W. Gorrod and P. Jacob, III., Elsevier, Amsterdam, 1999, pp. 225–264.
123. Bieber, A., G. Scherer, I. Hoepfner, F. Adlkofer, W.-D. Heller, J.E. Haddow, and G.J. Knight: The determination of nicotine and cotinine in human serum and urine: an interlaboratory study; Toxicol. Lett. 35 (1987) 45–52.
124. Feyerabend, C. and M.A.H. Russell: Assay of nicotine in biological materials: sources of contamination and their elimination; J. Pharm. Pharmacol. 32 (1980) 178–181.
125. Curvall, M., E. Kazemi-Vala, and C.R. Enzell: Simultaneous determination of nicotine and cotinine in plasma using capillary column gas chromatography with nitrogen-sensitive detection; J. Chromatogr. B 232 (1982) 283–293.
126. Jones, D., M. Curvall, L. Abrahamsson, E. Kazemi-Vala, and C. Enzell: Quantitative analysis of plasma nicotine using selected ion monitoring at high reso-lution. Biomed. Mass Spectrometry 9 (1982) 539–545.
127. Teeuwen, H.W.A., R.J.W. Aalders, and J.M. Van Rossum: Simultaneous estimation of nicotine and cotinine levels in biological fluids using high-resolution capillary-column gas chromatography combined with solid phase extraction work-up; Molecular Biol. Reports 13 (1989) 165–175.
128. Jacob, P. III., L. Yu, M. Wilson, and N.L. Benowitz: Selected ion monitoring method for determination of nicotine, cotinine and deuterium-labeled analogs: absence of an isotope effect in the clearance of (S)-nicotine-3’,3’-d2 in humans; Biol. Mass Spectrom. 20 (1991) 247–252.
129. Peach, H., G.A. Ellard, P.J. Jenner, and R.W. Morris: A simple, inexpensive urine test of smoking; Thorax 40 (1985) 351–357.
130. Ubbink, J.B., J. Lagendijk, and W.H.H. Vermaak: Simple high-performance liquid chromatographic method to verify the direct barbituric acid assay for urinary cotinine; J. Chromatogr. 620 (1993) 254–259.
131. Barlow, R.D., R.B. Stone, N.J. Wald, and E.V.J. Puha-kainen: The direct barbituric acid assay for nicotine metabolites in urine: a simple colorimetric test for the routine assessment of smoking status and cigarette smoke intake; Clin. Chim. Acta 165 (1987) 45–52.
132. Barlow, R.D., P.A. Thompson and R.B. Stone: Simultaneous determination of nicotine, cotinine and five additional nicotine metabolites in the urine of smokers using pre-column derivatization and high-performance liquid chromatography; J. Chromatogr. 419 (1987) 375–380.
133. Moore, J., M. Greenwood, and N. Sinclair: Automation of a high-performance liquid chromatographic assay for the determination of nicotine, cotinine and 3’-hydroxycotinine in human urine; J. Pharm. Biomed. Anal. 8 (1990) 1051–1054.
134. Puhakainen, E.V.J, R.D. Barlow, and J.T. Salonen: An automated colorimetric assay for urine nicotine meta-bolites: a suitable alternative to cotinine assays for the asssessment of smoking status; Clin. Chim. Acta 170 (1987) 255–262.
135. Pickert, A., T. Lingenfelser, C. Pickert, N. Birbaumer, D. Overkamp, and M. Eggstein: Comparison of a mechanized version of the “König” reaction and a fluorescence polarization immunoassay for the determination of nicotine metabolites in urine; Clin. Chem. Acta 217 (1993) 143–152.
136. Cope, G., P. Nayyar, R. Holder, J. Gibbons, and R. Bunce: A simple near-patient test for nicotine and its metabolites in urine to assess smoking habit; Clin. Chim. Acta 256 (1996) 135–149.
137. Parviainen, M.T. and R.D. Barlow: Assessment of ex-posure to environmental tobacco smoke using a high-performance liquid chromatographic method for the simultaneous determination of nicotine and two of its metabolites in urine; J. Chromatogr. 431 (1988) 216–221.
138. Rustemeier, K., D. Demetriou, G. Schepers, and P. Voncken: High-performance liquid chromatographic determination of nicotine and its urinary metabolites via their 1,3-diethyl-2-thiobarbituric acid derivatives; J. Chromatogr. 613 (1993) 95–103.
139. Chambers, K.L., G.A. Ellard, A.T. Hewson, and R.F. Smith: Urine test for the assessment of smoking status; Br. J. Biomed. Sci. 58 (2001) 61–65.
140. Langone, J.J., H.B. Gjika, and H. Van Vunakis: Nicotine and its metabolites. Radioimmunoassays for nicotine and cotinine; Biochemistry 12 (1973) 5025–5030.
141. Langone, J.J. and H. Van Vunakis: Radioimmunoassay of nicotine, cotinine and (-(-pyridyl)-(-oxo-N-methylbutyramide; Methods Enzymol. 84 (1982) 628–640.
142. Knight, G.J., P. Wylie, M.S. Holman, and J.E. Haddow: Improved 125I radioimmunoassay for cotinine by selective removal of bridge antibodies; Clin. Chem. 31 (1985) 118–121.
143. Bjercke, R.J., G. Cook, N. Rychlik, H.B. Gjika, H. Van Vunakis, and J.J. Langone: Stereospecific monoclonal antibodies to nicotine and cotinine and their use in enzyme-linked immunosorbent assays; J. Immunol. Methods 90 (1986) 203–213.
144. Langone, J.J., G. Cook, R.J. Bjercke, and M.H. Lif-schitz: Monoclonal antibody ELISA for cotinine in saliva and urine of active and passive smokers; J. Immunol. Methods 114 (1988) 73–78.
145. Benkirane, S., A. Nicolas, M.-M. Galteau, and G. Siest: Highly sensitive immunoassays for the determination of cotinine in serum and saliva. Comparison between RIA and an avidin-biotin ELISA; Eur. J. Clin. Chem. Clin. Biochem. 29 (1991) 405–410.
146. Hansel, M.C., F.J. Rowell, J. Landon, and A.M. Sidki: Single-reagent polarisation fluoroimmunoassay for cotinine (a nicotine metabolite) in urine; Ann. Clin. Biochem. 5 (1986) 596–602.
147. Alterman, A.I., P. Gariti, and R.S. Niedbala: Varying results for immunoassay screening kits for cotinine level; Psychol. Addict. Behav. 16 (2002) 256–259.
148. Niedbala, R.S., N. Haley, S. Kardos, and K. Kardos: Automated homogenous immunoassay analysis of cotinine in urine; J. Anal. Toxicol. 26 (2002) 166–170.
149. Van Vunakis, H., J.J. Langone, and A. Milunsky: Nicotine and cotinine in the amniotic fluid of smokers in the second trimester of pregnancy; Am. J. Obstet. Gynecol. 120 (1974) 64–66.
150. Haines, C.F., Jr., D.K. Mahajan, D. Miljikovif, M. Miljikovif, and E.S. Vesell: Radioimmunoassay of plasma nicotine in habituated and naive smokers; Clin. Pharmacol. Ther. 16 (1974) 1083–1090.
151. Castro, A., N. Monji, H. Ali, M. Yi, E.R. Bowman, and H. McKennis, Jr.: Nicotine antibodies: comparison of ligand specificities of antibodies produced against two nicotine conjugates; Eur. J. Biochem. 104 (1980) 331–340.
152. Hill, P. and H. Marquardt: Plasma and urine changes after smoking different brands of cigarettes; Clin. Pharm. 27 (1980) 652–658.
153. Hellberg, D., S. Nilsson, N.J. Haley, D. Hoffman, and E. Wynder: Smoking and cervical intraepithelial neo-plasia: nicotine and cotinine in serum and cervical mucus in smokers and nonsmokers; Am. J. Obstet. Gynecol. 158 (1988) 910–913.
154. Van Vunakis, H., H.B. Gijka, and J.J. Langone: Radioimunnoassay for nicotine and cotinine; in: Environmental carcinogens-methods of analysis and exposure measurement, Vol. 12: International Agency for Research on Cancer, edited by B. Seifert, H. van der Wiel, B. Bodet, and I.K. O'Neill, Lyon, 1993, pp. 293–299.
155. Pacifici, R., I. Altiere, L. Gandini, A. Lenzi, A.R. Passa, S. Pichini, M. Rosa, P. Zuccaro, and F. Dondero: Environmental tobacco smoke: nicotine and cotinine in semen; Environ. Res. 68 (1995) 69–72.
156. Sasson, I.M., N.J. Haley., D. Hoffmann, E.L. Wynder, D. Hellberg, and S. Nilsson: Cigarette smoking and neoplasia of the uterine cervix: smoker constituents in cervical mucus; N. Engl. J. Med. 312 (1985) 315–316.
157. Haley, N.J. and D. Hoffmann: Analysis for nicotine and cotinine in hair to determine cigarette smoker status; Clin. Chem. 31 (1985) 1598–1600.
158. Eliopoulos, C., J. Klein, K. Phan, B. Knie, M. Greenwald, D. Chitayat, and G. Koren: Hair concentrations of nicotine and cotinine in women and their new-born infants; JAMA 271 (1994) 621–623.
159. Woodruff, S.I., T.L. Conway, C.C. Edwards, and M.F. Hovell: Acceptability and validity of hair collection from Latino children to assess exposure to environ-mental tobacco smoke; Nicotine Tob. Res. 5 (2003) 375–385.
160. Ostrea, E.M., D.K. Knapp, A. Romero, M. Montes, and A.R. Ostrea: Meconium analysis to assess fetal ex-posure to nicotine by active and passive maternal smoking; J. Pediatr. 124 (1994) 471–476.
161. Heinrich-Ramm, R., R. Wegner, A.H. Garde, and X. Baur: Cotinine excretion (tobacco smoke biomarker) of smokers and nonsmokers: comprison of GC/MS and RIA results; Int. J. Hyg. Environ. Health 205 (2002) 493–499.
162. Jauniaux, E., B. Gulbis, G. Acharya, P. Thiry, and C. Rodeck: Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy; Obstet. Gynecol. 93 (1999) 25–29.
163. Bjercke, R.J., G. Cook, and J.J. Langone: Comparison of monoclonal and polyclonal antibodies to cotinine in nonisotopic and isotopic immunoassays; J. Immunol. Methods 96 (1987) 239–246.
164. Perkins, S.L., J.F. Livesey, E.A. Escares, J.M. Belcher, and D.K. Dudley: High-performance liquid-chromato-graphic method compared with a modified radioimmu-noassay of cotinine in plasma; Clin. Chem. 37 (1991) 1989–1992.
165. Vine, M.F., B.S. Hulka, B.H. Margolin, Y.K. Truong, P.-C. Hu, M.H. Schramm, J.D. Griffith, M. McCann, and R.B. Everson: Cotinine concentrations in semen, urine and blood of smokers and nonsmokers; Am. J. Public Health 83 (1993) 1335–1338.
166. Nafstad, P., J. Kongerud, G. Botton, P. Urdal, T. Sil-sand, B.S. Pedersen, and J.J.K. Jaakkola: Fetal exposure to tobacco smoke products, a comparison between self-reported maternal smoking and concentrations of cotinine and thiocyanate in cord serum; Acta Obstet. Gynecol. Scand. 75 (1996) 902–907.
167. Rosevear, S.K., D.W. Holt, T.D. Lee, W.C.L. Ford, P.G. Wardle, and M.G.R. Hull: Smoking and decreased ferti-lization rates in vitro; Lancet 340 (1992) 1195–1196.
168. Zenzes, M.T., T.E. Reed, P. Wang, and J. Klein: Cotinine, a major metabolite of nicotine, is detectable in follicular fluids of passive smokers in in vitro fertilization therapy; Fertil. Steril. 66 (1996) 614–619.
169. Younglai, E.V., W.G. Foster, E.G. Hughes, K. Trim, and J.F. Jarrell: Levels of environmental contaminants in human follicular fluid, serum and seminal plasma of couples undergoing in vitro fertilization; Arch. Environ. Contam. Toxicol. 43 (2002) 121–126.
170. Knight, J.M., C. Eliopoulos, J. Klein, M. Greenwald, and G. Koren: Passive smoking in children. Racial differences in systemic exposure to cotinine by hair and urine analysis; Chest 109 (1996) 446–450.
171. Zenzes, M.T., R. Bielecki, and T.E. Reed: Detection of benzo(a)pyrene diol epoxide-DNA adducts in sperm of men exposed to cigarette smoke; Fertil. Steril. 72 (1999) 330–335.
172. Wong, W.Y., C.M.G. Thomas, H.M.W.M. Merkus, G.A. Zielhuis, W.H. Doesburg, and R.P.M. Steegers-Theunissen: Cigarette smoking and the risk of male factor subfertility: minor association between cotinine in seminal plasma and semen morphology; Fertil. Steril. 74 (2000) 900–935.
173. Van Vunakis, H., H.B. Gijka, and J.J. Langone: Radio-immunoassay for nicotine and cotinine; in: Environ-mental carcinogens-methods of analysis and exposure measurement, Vol. 9, International Agency for Research on Cancer, edited by I.K. O'Neill, K.D. Brunnemann, B. Bodet, and D. Hoffmann, Lyon, 1987, pp. 317–330.
174. Watts, R.R., J.J. Langone, G.J. Knight, and J. Lewtas: Cotinine analytical workshop report: consideration of analytical methods for determining cotinine in human body fluids as a measure of passive exposure to tobacco smoke; Environ. Health Perspect. 84 (1990) 173–182.
175. Schepers, G. and R.-A. Walk: Cotinine determination by immunoassays may be influenced by other nicotine metabolites; Arch. Toxicol. 62 (1988) 395–397.
176. Zuccaro, P., S. Pichini, I. Altieri, M. Rosa, M. Pelle-grini, and R. Pacifici: Interference of nicotine meta-bolites in cotinine determination by RIA; Clin. Chem. 43 (1997) 181–182.
177. Hansen, Å.M., A.H. Garde, J.M. Christensen, N. Eller, L.E. Knudsen, and R. Heinrich-Ramm: Reference interval and subject variation in excretion of urinary metabolites of nicotine from non-smoking healthy subjects in Denmark; Clin. Chim. Acta 304 (2001) 125–132.
178. Fergusson, B.B., D.J. Wilson, and W. Schaffner: Determination of nicotine concentrations in human milk; Am. J. Dis. Child. 130 (1976) 837–839.
179. Hengen, N. and M. Hengen: Gas-liquid chromato-graphic determination of nicotine and cotinine in plasma; Clin. Chem. 24 (1978) 50–53.
180. Feyerabend, C. and M.A.H. Russell: Improved gas-chromatographic method and micro-extraction technique for the measurement of nicotine in biological fluids; J. Pharm. Pharmacol. 31 (1979) 73–76.
181. Jacob, P., III., M. Wilson, and N.L. Benowitz: Im-proved gas chromatographic method for the deter-mination of nicotine and cotinine in biologic fluids; J. Chromatogr. 222 (1981) 61–70.
182. Jacob, P., III., A.T. Shulgin, L. Yu, and N.L. Benowitz: Determination of the nicotine metabolite trans-3’-hydroxycotinine in urine of smokers using gas chro-matography with nitrogen-selective detection or selected ion monitoring; J. Chromatogr. 583 (1992) 145–154.
183. Kogan, M.J., K. Verebey, J.H. Jaffee, and S.J. Mulé: Simultaneous determination of nicotine and cotinine in human plasma by nitrogen detection gas-liquid chroma-tography; J. Forensic Sci. 26 (1981) 6–11.
184. Stehlik, G., J. Kainzbauer, H. Tausch, and O. Richter: Improved method for routine determination of nicotine and its main metabolites in biological fluids; J. Chromatogr. 232 (1982) 295–303.
185. Davis, R.A.: The determination of nicotine and cotinine in plasma; J. Chrom. Sci. 24 (1986) 134–141.
186. Voncken, P., G. Schepers, and K.H. Schäfer: Capillary gas chromatographic determination of trans-3’-hydroxy-cotinine simultaneously with nicotine and cotinine in urine and blood samples; J. Chromatogr. 479 (1989) 410–418.
187. Petrakis, N.L., L.D. Gruenke, T.C. Beelen, N. Castag-noli, and J.C. Craig: Nicotine in breast fluid of non-lactating women; Science 199 (1978) 303–304.
188. Davoli, E., L. Stramare, R. Fanelli, L. Diomede, and M. Salmona: Rapid solid-phase extraction method for automated gas chromatographic-mass spectrometric determination of nicotine in plasma; J. Chromatogr. B 707 (1998) 312–316.
189. Daenens, P., L. Laruelle, K. Callewaert, P. De Schepper, R. Galeazzi, and J. van Rossum: Determi-nation of cotinine in biological fluids by capillary gas chromatography-mass spectrometry-selected-ion monitoring; J. Chromatogr. 342 (1985) 79–87.
190. Skarping, G., S. Willers, and M. Dalene: Determination of the cotinine in urine using glass capillary gas chromatography and selective detection, with special reference to the biological monitoring of passive smoking; J. Chromatogr. 454 (1988) 293–301.
191. McAdams, S.A. and M.L. Cordeiro: Simple selected ion monitoring capillary gas chromatographic-mass spectrometric method for the determination of cotinine in serum, urine and oral samples; J. Chromatogr. 615 (1993) 148–153.
192. Lewis, S.J., N.M. Cherry, R.M.C.L. Niven, P.V. Barber, K. Wilde, and A.C. Povey: Cotinine levels and self-reported smoking status in patients attending a bronchoscopy clinic; Biomarkers 8 (2003) 218–228.
193. James, H., Y. Tizabi, and R. Taylor: Rapid method for the simultaneous measurement of nicotine and cotinine in urine and serum by gas chromatography-mass spectrometry; J. Chromatogr. B 708 (1998) 87–93.
194. Shin, H.S., J.G. Kim, Y.J. Shin, and S.H. Jee: Sensitive and simple method for the determination of nicotine and cotinine in human urine, plasma and saliva by gas chromatography – mass spectrometry; J. Chromatogr. B 769 (2002) 177–183.
195. Cognard, E. and C. Staub: Determination of nicotine and its major metabolite cotinine in plasma or serum by gas chromatography-mass spectrometry using ion-trap detection; Clin. Chem. Lab. Med. 41 (2003) 1599–1607.
196. Tora½o, J.S. and H.J.M. van Kan: Simultaneous determination of the tobacco smoke uptake parameters nicotine, cotinine and thiocyanate in urine, saliva and hair, using gas chromatography-mass spectrometry for characterisation of smoking status of recently exposed subjects; Analyst 128 (2003) 838–843.
197. Mousa, S., G.R. Van Loon, A.A. Houdi, and P.A. Crooks: High-performance liquid chromatography with electrochemical detection for the determination of nicotine and N-methylnicotinium ion; J. Chromatogr. 347 (1985) 405–410.
198. Chien, C., J.N. Diana, and P.A. Crooks, High-perfor-mance liquid chromatography with electrochemical detection for the determination of nicotine in plasma; J. Pharm. Sci. 77 (1988) 277–279.
199. Mahoney, G.N. and W. Al-Delaimy: Measurement of nicotine in hair by reversed-phase high-performance liquid chromatography with electrochemical detection; J. Chromatogr. 753 (2001) 179–187.
200. Machacek, D.A. and N.-S. Jiang: Quantification of cotinine in plasma and saliva by liquid chromato-graphy; Clin. Chem. 32 (1986) 979–982.
201. Shen, H., S. Chia, Z. Ni, A. New, B. Lee, and C. Ong: Detection of oxidative damage in human sperm and the association with cigarette smoking; Reprod. Toxicol. 11 (1997) 675–680.
202. Greaves, R., L. Trotter, S. Brennecke, and E. Janus: A simple high-pressure liquid chromatography cotinine assay: validation of smoking status in pregnant women; Ann. Clin. Biochem. 38 (2001) 333–338.
203. Baranowski, J., G. Pochopie½, and I. Baranowska: Determination of nicotine, cotinine and caffeine in meconium using high-performance liquid chromato-graphy; J. Chromatogr. B 707 (1998) 317–321.
204. Harlharan, M., T. VanNoord, and J.F. Greden: A high-performance liquid chromatographic method for routine simultaneous determination of nicotine and cotinine in plasma; Clin. Chem. 34 (1988) 724–729.
205. Page-Sharp, M., T.W. Hale, L.P. Hackett, J.H. Kristen-sen, and K.F. Ilett: Measurement of nicotine and coti-nine in human milk by high-performance liquid chro-matography with ultraviolet absorbance detection; J. Chromatogr. B 796 (2003) 173–180.
206. Ghosheh, O.H., D. Browne, T. Rogers, J. de Leon, L.P. Dwoskin, and P.A. Crooks: A simple high performance liquid chromatographic method for the quantification of total cotinine, total 3’-hydroxycotinine and caffeine in the plasma of smokers; J. Pharm. Biomed. Anal. 23 (2000) 543–549.
207. Cundy, K.C. and P.A. Crooks: High-performance liquid chromatographic method for the determination of N-methylated metabolites of nicotine; J. Chromatogr. 306 (1984) 291–301.
208. Kyerematen, G.A., L.H. Taylor, J.D. deBethizy, and E.S. Vesell: Radiometric-high-performance liquid chro-matographic assay for nicotine and twelve of its metabolites; J. Chromatogr. 419 (1987) 191–203.
209. Pacifici, R., I. Altiere, L. Gandini, A. Lenzi, S. Pichini, M. Rosa, P. Zuccaro, and F. Dondero: Nicotine, cotinine and trans-3’-hydroxycotinine levels in seminal plasma of smokers: effects on sperm parameters; Ther. Drug Monit. 15 (1993) 358–363.
210. McManus, K.T., J.D. deBethizy, D.A. Garteiz, G.A. Kyerematen, and E.S. Vesell: A new quantitative thermospray LC-MS method for nicotine and its meta-bolites in biological fluids; J. Chrom. Sci. 28 (1990) 510–516.
211. Byrd, G.D., M.S. Uhrig, J.D. deBethizy, W.S. Caldwell, P.A. Crooks, A. Ravard, and R.M. Riggs: Direct determination of cotinine-N-glucuronide in urine using thermospray liquid chromatography/mass spectrometry; Biol. Mass Spectrom. 23 (1994) 103–107.
212. Bentley, M.C., M. Abrar, M. Kelk, J. Cook, and K. Phillips: Validation of an assay for the determination of cotinine and 3-hydroxycotinine in human saliva using automated solid-phase extraction and liquid chromato-graphy with tandem mass spectrometry detection; J. Chromatogr. 723 (1999) 185–194.
213. Byrd, G.D., R.A. Davis, and M.W. Ogden: A rapid LC-MS-MS method for the determination of nicotine and cotinine in serum and saliva samples from smokers: Validation and comparison with a radioimmunoassay method; J. Chrom. Sci. 43 (2005) 133–140.
214. Bernert, J.T., Jr., J.E. McGuffey, M.A. Morrison, and J.L. Pirkle: Comparison of serum and salivary cotinine measurements by a sensitive high-performance liquid chromatographytandem mass spectrometry method as an indicator of exposure to tobacco smoke among smokers and nonsmokers; J. Anal. Toxicol. 24 (2000) 333–339.
215. Bernert, J.T., W.E. Turner, J.L. Pirkle, C.S. Sosnoff, J.R. Akins, M.K. Waldrep, Q. Ann, T.R. Covey, W.E. Whitfield, E.W. Gunter, B.B. Miller, D.G. Patterson, Jr., L.L. Needham, W.H. Hannon, and E.J. Sampson: Development and validation of sensitive method for determination of serum cotinine in smokers and nonsmokers by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry; Clin. Chem. 43 (1997) 2281–2291.
216. Kellogg, M.D., J. Behaderovic, O. Bhalala, and N. Rifai: Rapid and simple tandem mass spectrometry method for determination of serum cotinine concen-tration; Clin. Chem. 50 (2004) 2157–2159.
217. Xu, A.S., L.L. Peng, J.A. Havel, M.E. Peterson, J.A. Fiene, and J.D. Hulse: Determination of nicotine and cotinine in human plasma by liquid chromatographytandem mass spectrometry with atmospheric pressure chemical ionization interface; J. Chromatogr. B. 682 (1996) 249–257.
218. Taylor, P.J., K.K. Forrest, P.G. Landsberg, C. Mitchell, and P.I. Pillans: The measurement of nicotine in human plasma by high-performance liquid chromatography-electrospraytandem mass spectrometry; Ther. Drug Monit. 26 (2004) 563–568.
219. Moyer, T.P., J.R. Charlson, R.J. Enger, L.C. Dale, J.O. Ebbert, D.R. Schroeder, and R.D. Hurt: Simultaneous analysis of nicotine, nicotine metabolites and tobacco alkaloids in serum or urine by tandem mass spectro-metry, with clinically relevant metabolic profiles; Clin. Chem. 48 (2002) 1460–1471.
220. Xu, X., M.M. Iba, and C.P. Weisel: Simultaneous and sensitive measurement of anabasine, nicotine and nico-tine metabolites in human urine by liquid chromato-graphytandem mass spectrometry; Clin. Chem. 50 (2004) 2323–2330.
221. Yamanaka, H., M. Nakajima, K. Nishimura, R. Yoshida, T. Fukami, M. Katoh, and T. Yokoi: Metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted; Eur. J. Pharm. Sci. 22 (2004) 419–425.
222. Heavner, D.L., J.D. Richardson, W.T. Morgan, and M.W. Ogden: Validation and application of a method for the determination of nicotine and five major metabolites in smokers’ urine by solid-phase extraction and liquid chromatographytandem mass spectrometry; Biomed. Chromatogr. 19 (2005) 312–328.
223. Karnes, H.T., J.R. James, C. March, D.E. Leyden, and K. Koller: Assessment of nicotine uptake from cigarette smoke: comparison of a colorimetric test strip (Nic-Check ITM) and gas chromatography/mass selective detector; Biomarkers 6 (2001) 388–399.
224. Gariti, P., D.I. Rosenthal, K. Lindell, J. Hansen-Fla-schen, J. Shrager, C. Lipkin, A.I. Alterman, and L.R. Kaiser: Validating a dipstick method for detecting recent smoking; Cancer Epidemiol. Biomarkers Prev. 11 (2002) 1123–1125.
225. Parker, D.R., T.M. Lasater, R. Windsor, J. Wilkins, D.I. Upegui, and J. Heimdal: The accuracy of self-reported smoking status assessed by cotinine test strips; Nicotine Tob. Res. 4 (2002) 305–309.
226. Berry, D.J. and J. Grove: Inproved chromatographic techniques and their interpretation for the screening of urine from drug dependent subjects; J. Chromatogr. 61 (1971) 111–116.
227. Bazylak, G., H. Brózik, and W. Sabanty: Combined SPE and HPTLC as a screening assay of urinary cotinine from male adolescents exposed to environ-mental tobacco smoke; Polish J. Environ. Studies 9 (2000) 113–123.
228. Palmer, M.E., R.F. Smith, K. Chamber, and L.W. Tetler: Separation of nicotine metabolites by capillary zone electrophoresis and capillary zone electropho-res/mass spectrometry; Rapid Comm. Mass Spectrom. 15 (2001) 224–231.
229. Baidoo, E.E.K., M.R. Clench, R.F. Smith, and L.W. Tetler: Determination of nicotine and its metabolites in urine by solid-phase extraction and sample stacking capillary electrophoresis-mass spectrometry; J. Chromatogr. B 796 (2003) 303–313.
230. Jarvis, M.J. and M.A.H. Russell: Passive exposure to tobacco smoke; Br. Med. J. 291 (1985) 1646.
231. Curvall, M., E. Kazemi-Vala, J. Wahren, and C. Enzell: Concentration of cotinine body fluids as a measure of nicotine intake by nonsmokers; in: The Pharmacology of Nicotine, edited by M.J. Rand and K. Thurau, IRL Press, Oxford, 1988, pp. 32–33.
232. Jarvis, M.J., P. Primatesta, B. Erens, C. Feyerabend, and A. Bryant: Measuring nicotine intake in population sur-veys: comparability of saliva cotinine and plasma coti-nine estimates; Nicotine Tob. Res. 5 (2003) 349–355.
233. Wewers, M.E., K.L. Ahijevych, R.K. Dhatt, R.M. Guthrie, P. Kuun, L. Mitchell, M.L. Moeschberger, and M.S. Chen Jr.: Cotinine levels in Southeast Asian smokers; Nicotine Tob. Res. 2 (2000) 85–91.
234. Jarvis, M., H. Tunstall-Pedoe, C. Feyerabend, C. Vesey, and Y. Salloojee: Biochemical markers of smoke absorption and self reported exposure to passive smoking; J. Epidemiol. Commun. Health 38 (1984) 335–339.
235. Jarvis, M.J., M.A.H. Russell, N.L. Benowitz, and C. Feyerabend: Elimination of cotinine from body fluids: implications for noninvasive measurement of tobacco smoke exposure; Am. J. Public Health 78 (1988) 696–698.
236. Wall, M.A., J. Johnson, P. Jacob, and N.L. Benowitz: Cotinine in the serum, saliva and urine of nonsmokers, passive smokers and active smokers; Am. J. Public Health 78 (1988) 699–701.
237. Coultas, D.B., J.M. Samet, J.F. McCarthy, and J.D. Spengler: Variability of measures of exposure to environmental tobacco smoke in the home; Am. Rev. Respir. Dis. 142 (1990) 602–606.
238. Berlin, I., A. Radzius, J.E. Henningfield, and E.T. Moolchan: Correlates of expired air carbon monoxide: effect of ethnicity and relationship with saliva cotinine and nicotine; Nicotine Tob. Res. 3 (2001) 325–331.
239. Dolcini, M.M., N.E. Adler, P. Lee, and K.E. Bauman: An assessment of the validity of adolescent self-reported smoking status using three biological markers; Nicotine Tob. Res. 5 (2003) 473–383.
240. Stookey, G.K., B.P. Katz, B.L. Olsen, C.A. Drook, and S.J. Cohen: Evaluation of biochemical validation measures in determination of smoking status; J. Dent. Res. 66 (1987) 1597–1601.
242. Cummings, S.R. and R.J. Richard: Optimum cutoff points for biochemical validation of smoking status; Am. J. Public Health 78 (1988) 574–575.
243. Wagenknecht, L.E., G.L. Burke, L.L. Perkins, N.J. Haley, and G.D. Friedman: Misclassification of smoking status in the CARDIA study: a comparison of self-report with serum cotinine levels; Am. J. Public Health 82 (1992) 33–36.
244. Caraballo, R.S., G.A. Giovino; and T.F. Pechacek: Self-reported cigarette smoking vs. serum cotinine among U.S. adolescents; Nicotine Tob. Res. 6 (2004) 19–25.
245. McNeill, A.D., M.J. Jarvis, R. West, M.A.H. Russell, and A. Bryant: Saliva cotinine as an indicator of cigarette smoking in adolescents; Br. J. Addict. 82 (1987) 1355–1360.
246. Wagenknecht, L.E., G.R. Cutter, N.J. Haley, S. Sidney, T.A. Manolio, G.H. Hughes, and D.R. Jacob: Racial differences in serum cotinine levels among smokers in the Coronary Artery Risk Development in (Young) Adults Study; Am. J. Public Health 80 (1990) 1053–1056.
247. English, P.B., B. Eskenazi, and R.E. Christianson: Black-white differences in serum cotinine levels among pregnant women and subsequent effects on infant birthweight; Am. J. Public Health 84 (1994) 1439–1443.
248. Pérez-Stable, E.J., G. Marín, B.V. Marín, and N.L. Benowitz: Misclassification of smoking status by self-reported cigarette consumption; Am. Rev. Resp. Dis. 145 (1992) 53–57.
249. Caraballo, R.S., G.A. Giovino, T.F. Pechacek, and P.D. Mowery: Factors associated with discrepancies between self-reports on cigarette smoking and measured serum cotinine levels among persons aged 17 years or older; Am. J. Epidemiol. 153 (2001) 807–814.
250. Owen, L. and A. McNeill: Saliva cotinine as indicator of cigarette smoking in pregnant women; Addiction 96 (2001) 1001–1006.
251. Jacob, P., III., L. Yu, A.T. Shulgin, and N.L. Benowitz: Minor tobacco alkaloids as biomarkers for tobacco use: comparison of users of cigarette, smokeless tobacco, cigar and pipes; Am. J. Public Health 89 (1999) 731–736.
252. Jacob, P., III., D. Hatsukami, H. Severson, S. Hall, L. Yu, and N.L. Benowitz: Anabasine and anatabine as biomarkers for tobacco use during nicotine replacement therapy; Cancer Epidemiol. Biomarker Prev. 11 (2002) 1668–1673.
253. Feyerabend, C. and M.A.H. Russell: Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum; Br. J. clin. Pharmac. 5 (1978) 293–297.
254. Benowitz, N.L., P. Jacob, III., R.T. Jones, and J. Rosenberg: Interindividual variability in the metabolism and cardiovascular effects of nicotine in man; J. Phar-macol. Exp. Ther. 221 (1982) 368–372.
255. Benowitz, N.L., F. Kuyt, P. Jacob, III., R.T. Jones, and A.-L. Osman: Cotinine disposition and effects; Clin. Pharmacol. Ther. 34 (1983) 604–611.
256. Isaac, P.F. and M.J. Rand, Cigarette smoking and plasma levels of nicotine; Nature 236 (1972) 308–310.
257. Foulds, J., A. Bryant, J. Stapleton, M.J. Jarvis, and M.A.H. Russell: The stability of cotinine in unfrozen saliva mailed to the laboratory; Am. J. Public Health 81 (1994) 1182–1183.
258. Vartiainen, E., T. Seppälä, P. Lillsunde, and P. Puska: Validation of self reported smoking by serum cotinine measurement in a community-based study; J. Epide-miol. Community Health 56 (2000) 167–170.
259. Pérez-Stable, E.J., N.L. Benowitz, and G. Marín: Is serum cotinine a better measure of cigarette smoking than self-report?; Prev. Med. 24 (1995) 171–179.
260. Benowitz, N.L. and D.S. Sharp: Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers; Circulation 80 (1989) 1309–1312.
261. Caraballo, R.S., G.A. Giovino, T.F. Pechacek, P.D. Mowery, P.A. Richter, W.J. Strauss, D.J. Sharp, M.P. Eriksen, J.L. Pirkle, and K.R. Maurer: Racial and ethnic differences in serum cotinine levels of cigarette smokers; JAMA 280 (1998) 135–139.
262. Wagenknecht, L.E., T.A. Manolio, S. Sidney, G.L. Burke, and N.J. Haley: Environmental tobacco smoke exposure as determined by cotinine in black and white young adults: the CARDIA Study; Environ. Res. 63 (1993) 39–46.
263. Crawford, F.G., J. Mayer, R.M. Santella, T.B. Cooper, R. Ottman, W.Y. Tsai, G. Simon-Cereijido, M. Wang, D. Tang, and F.P. Perera: Biomarkers of environmental tobacco smoke in pre-school children and their mothers; J. Natl. Cancer Inst. 86 (1994) 1398–1402.
264. Pirkle, J.L., K.M. Flegal, J.T. Bernert, D.J. Brody, R.A. Etzel, and K.R. Maurer: Exposure of the US population to environmental tobacco smoke. The Third National Health and Nutrition Examination Survey 1988 to 1991; JAMA 275 (1996) 1233–1240.
265. Jarvis, M.J., C. Feyerabend, A. Bryant, B. Hedges, and P. Primatesta: Passive smoking in the home: plasma cotinine concentrations in non-smokers with smoking partners; Tobacco Control 10 (2001) 368–374.
266. Kaufman, F.L., M. Kharrazi, G.N. DeLorenze, B. Eskenazi, and J.T. Bernert: Estimation of environ-mental tobacco smoke exposure during pregnancy using a single question on household smokers verses serum cotinine; J. Exp. Anal. Environ. Epidemiol. 12 (2002) 286–295.
267. Pattishall, E.N., G.L. Strope, R.A. Etzel, R.W. Helms, N.J. Haley, and F.W. Denny: Serum cotinine as a measure of tobacco smoke exposure in children; Am. J. Dis. Child. 139 (1985) 1101–1104.
268. Mannino, D.M., R. Caraballo, N. Benowitz, and J. Repace: Predictors of cotinine levels in US children. Data from the Third National Health and Nutrition Examination Survey; Chest 120 (2001) 718–724.
269. Mercelina-Roumans, P.E.A.M., H. Schouten, J.M.H. Ubachs, and J.W.J. van Wersch: Cotinine concen-trations in plasma of smoking pregnant women and their infants; Eur. J. Clin. Chem. Biochem. 34 (1996) 525–528.
270. Pichini, S., X. Basagana, R. Pacifici, O. Garcia, C. Puig, O. Vall, J. Harris, P. Zuccaro, J. Segura, and J. Sunyer: Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy; Env. Health Perspect. 108 (2000) 1079–1083.
271. Pojer, R., J.B. Whitfield, V. Poulos, I.F. Eckhard, R. Richmond, and W.J. Hensley: Carboxyhemoglobin, cotinine and thiocyanate assay compared for distinguishing smokers from non-smokers; Clin. Chem. 30 (1984) 1377–1380.
272. de Leon, J., F.J. Diaz, T. Rogers, D. Browne, L. Dinsmore, O.H. Gosheh, L.P. Dwoskin, and P.A. Crooks: Plasma cotinine 3’-hydroxycotinine and their glucuronides in white and black smokers; J. Clin. Psychopharmacol. 23 (2003) 209–211.
273. Galeazzi, R.L., P. Daenens, and M. Gugger: Steady-state concentration of cotinine as a measure of nicotine-intake by smokers; Eur. J. Clin. Pharmacol. 28 (1985) 301–304.
274. Ashton, H., R. Stepney, and J.W. Thompson: Self-titration by cigarette smokers; Br. Med. J. 2 (1979) 357–360.
275. Zacny, J.P., M.L. Stitzer, F.J. Brown, J.E. Yingling, and R.R. Griffiths: Human cigarette smoking: effects of puff and inhalation parameters on smoke exposure; J. Pharmacol. Expt. Ther. 240 (1987) 554–564.
277. Höfer, I., R. Nil, and K. Bättig: Nicotine yield as determinant of smoke exposure indicators and puffing behavior; Pharmacol. Biochem. Behav. 40 (1991) 139–149.
278. Patterson, F., N. Benowitz, P. Shields, V. Kaufmann, C. Jepson, P. Wileyto, S. Kucharski, and C. Lerman: Indi-vidual differences in nicotine intake per cigarette; Can-cer Epidemiol; Biomarkers Prev. 12 (2003) 468–471.
279. Malson, J.L., E.M. Lee, R. Murty, E.T. Moolchan, and W.B. Pickworth: Clove cigarette smoking: biochemical, physiological and subjective effects; Pharmacol. Biochem. Behav. 74 (2003) 739–745.
280. Baker, R.R. and M. Dixon: The retention of tobacco smoke constituents in the human respiratory tract; Inhalation Toxicol. 17 (2006) 1–39.
281. Olivieri, M., A. Poli, P. Zuccaro, M. Ferrari, G. Lampronti, R. de Marco, V.L. Cascio, and R. Pacifici: Tobacco smoke exposure and serum cotinine in a random sample of adults living in Verona, Italy; Arch. Environ. Health 57 (2002) 355–359.
282. Rosa, M., R. Pacifici, I. Altieri, S. Pichini, G. Ottaviani, and P. Zuccaro: How the steady-state cotinine concen-tration in cigarette smokers is directly related to nico-tine intake; Clin. Pharmacol. Ther. 52 (1992) 324–329.
283. SRNT Subcommittee on Biochemical Verification: Biochemical verification of tobacco use and cessation; Nicotine Tob. Res. 4 (2002) 149–159.
284. US Public Health Service: Healthy People 2010: National Health Promotion and Disease Prevention Objectives [full report, with commentary]; Department of Health and Human Services, Washington DC, 2000.
285. Assaf, A.R., D. Parker, K.L. Lapane, J.L. McKenney, and R.A. Carleton: Are gender differences in self-reported smoking practices? Correlation with thio-cyanate and cotinine levels in smokers and nonsmokers from the Pawtucket Heart Health Program; J. Women's Health 11 (2002) 899–906.
286. A Report of the Surgeon General: Tobacco Use Among U.S. Racial/Ethnic Minoroty Groups – African Ameri-cans, American Indians and Alaska Natives, Asian Americans and Pacific Islanders and Hispanics; Rock-ville, Maryland, US Department of Health and Human Services, 1989.
287. de Leon, J., F.J. Diaz, T. Rogers, D. Browne, L. Dins-more, O.H. Gosheh, L.P. Dwoskin, and P.A. Crooks: Total cotinine in plasma: a stable biomarker for expo-sure to tobacco smoke; J. Clin. Psychopharmacol. 22 (2002) 496–501.
288. Lambers, D.S. and K.E. Clark: The maternal and fetal physiologic effects of nicotine; Semin. Perinatol. 20 (1996) 115–126.
289. Bearer, C., R.K. Emerson, M.A. O'Riordan, E. Roit-man, and C. Shackleton: Maternal tobacco smoke expo-sure and persistent pulmonary hypertension of the new-born; Environ. Health Perspect. 105 (1997) 202–206.
290. Benowitz, N.L.: Biomarkers of environmental tobacco smoke exposure; Environ. Health Perspect. 107 (1999) 349–355.
291. Feyerabend, C., T. Higenbottam, and M.A.H. Russell: Nicotine concentrations in urine and saliva of smokers and non-smokers; Br. Med. J. 284 (1982) 1002–1004.
292. Abrams, D.B., M.J. Follick, L. Biener, K.B. Carey, and J. Hitti: Saliva cotinine as a measure of smoking status in field settings; Am. J. Public Health 77 (1987) 846–848.
293. Lee, P.N.: Lung cancer and passive smoking: asso-ciation an artefact due to missclasification of smoking habits?; Toxicol. Lett. 35 (1987) 157–162.
294. Etter, J.-F., T.V. Perneger, and A. Ronchi: Collecting saliva samples by mail; Am. J. Epidemiol. 147 (1998) 141–146.
295. Etter, J.-F., T. Vu Duc, and T.V. Perneger: Saliva cotinine levels in smokers and nonsmokers; Am. J. Epidemiol. 151 (2000) 251–258.
296. Schneider, N.G., P. Jacob III., F. Nilsson, S.J. Leischow, N.L. Benowitz, and R.E. Olmstead: Saliva cotinine levels as a function of collection method; Addiction 92 (1997) 347–351.
297. Feyerabend, C. and M.A.H. Russell: A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids; J. Pharm. Pharmacol. 42 (1990) 450–452.
298. Delifino, R.J., P. Ernst, M.S. Jaakkola, S. Solomon, and M.R. Becklake: Questionnaire assessments of recent exposure to environmental tobacco smoke in relation to salivary cotinine; Eur. Respir. J. 6 (1993) 1104–1108.
299. Jarvis, M.J., E. Goddard, V. Higgins, C. Feyerabend, A. Bryant, and D.G. Cook: Children's exposure to passive smoking in England since the 1980s: cotinine evidence from population surveys; Br. Med. J. 321 (2000) 343–345.
300. Pierce, J.P., T. Dwyer, E. DiGiusto, T. Carpenter, C. Hannam, A. Amin, C. Yong, G. Sarfaty, J. Shaw, and N. Burke: Cotinine validation of self-reported smoking in commercially run community surveys; J. Chronic Dis. 40 (1987) 689–695.
301. Etzel, R.A.: A review of the use of saliva cotinine as a marker of tobacco smoke exposure; Prev. Med. 19 (1990) 190–197.
302. Cummings, K.M., S.J. Markello, M. Mahoney, A.K. Bhargava, P.D. McElroy, and J.R. Marshall: Measure-ment of current exposure to environmental tobacco smoke; Arch. Environ. Health 45 (1990) 74–79.
303. Beckett, A.H., M. Rowland, and E.J. Triggs: Significance of smoking in investigations of urinary excretion rates of amines in man; Nature 207 (1965) 200–201.
304. Labrecque, M., S. Marcoux, J.-P. Weber, J. Fabia, and L. Ferron: Feeding and urine cotinine values in babies whose mothers smoke; Pediatrics 83 (1989) 93–97.
305. Thompson, S.G., R.D. Barlow, N.J. Wald, and H. Van Vunakis: How should urinary cotinine concentrations be adjusted for urinary creatinine concentration? Clin. Chim. Acta 187 (1990) 289–295.
306. Dahlström, A., B. Lundell, M. Curvall, and L. Thapper: Nicotine and cotinine concentrations in the nursing mother and her infant; Acta Paediatr. Scand. 79 (1990) 142–147.
307. Köhler, E., D. Bretschneider, A. Rabsilber, W. Weise, and G. Jorch: Assessment of prenatal smoke exposure by determining nicotine and its metabolites in maternal and neonatal urine; Human Exp. Toxicol. 20 (2001) 1–7.
308. Cornelius, M.D., L. Goldschmidt, and D.A. Dempsey: Environmental tobacco smoke exposure in low-income 6-year-olds: Parent report and urine cotinine measures; Nicotine Tob. Res. 5 (2003) 333–339.
309. Haddow, J.E., G.J. Knight, G.E. Palomaki, L.M. Neveux, and B.A. Chilmonczyk: Replacing creatinine measurements with specific gravity values to adjust urine cotinine concentrations; Clin. Chem. 40 (1994) 562–564.
310. Heavner, D.L., W.T. Morgan, S.B. Sears, J.D. Richardson, G.D. Byrd, and M.W. Ogden: Effect of cre-atinine and specific agravity normalization techniques on xenobiotic biomarkers in smokers’ spot and 24-h urines; J. Pharm. Biomed. Anal. 40 (2006) 928–942.
311. Jatlow, P., S. McKee, and S.S. O'Malley: Correction of urine cotinine concentrations for creatinine excretion: is it useful? Clin. Chem. 49 (2003) 1932–1934.
312. Luck, W. and H. Nau: Nicotine and cotinine concen-trations in serum and milk of nursing smokers; Br. J. clin. Pharmac. 18 (1984) 9–15.
313. Hagan, R.L., J.M. Ramos Jr., and P.M. Jacob III.: Increasing urinary cotinine concentrations at elevated temperatures: the role of conjugated metabolites; J. Pharmaceutical Biomedical Anal. 16 (1997) 191–197.
314. Riboli, E., N.J. Haley., F. De Waard, and R. Saracci: Validity of urinary biomarkers of exposure to tobacco smoke following prolonged storage; Int. J. Epidemiol. 24 (1995) 354–358.
315. Jacqz-Aigrain, E., D. Zhang, G. Maillard, D. Luton, J. André, and J.F. Oury: Maternal smoking during preg-nancy and nicotine and cotinine concentrations in maternal and neonatal hair; Br. J. Obstet. Gynaecol. 109 (2002) 909–911.
316. Riboli, E., N.J. Haley., J. Trédaniel, R. Saracci, S. Preston-Martin, and D. Trichopoulos: Misclassification of smoking status among women in relation to exposure to environmental tobacco smoke; Eur. Respir. J. 8 (1995) 285–290.
317. Nafstad, P., G. Botten, J.A. Hagen, K. Zahlsen, O.G., Nilsen, T. Silsand, and J. Kongerud: Comparison of three methods for estimating environmental tobacco smoke exposure among children aged between 12 and 36 months; Int. J. Epidemiol. 24 (1995) 88–94.
318. Matt, G.E., D.R. Wahlgren, M.F. Hovell, J.M. Zakarian, J.T. Bernert, S.B. Meltzer, J.L. Pirkle, and S. Caudill: Measuring environmental tobacco smoke exposure in infants and young children through urine cotinine and memory-based parental reports: empirical findings and discussion; Tobacco Control 8 (1999) 282–289.
319. Luck, W. and H. Nau: Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers; J. Pediatr. 107 (1985) 816–820.
320. Woodward, A., N. Grgurinovich, and P. Ryan: Breast feeding and smoking hygiene: major influences on cotinine in urine of smokers’ infants; J. Epidemiol. Community Health 40 (1986) 309–315.
321. Thompson, S.G., R. Stone, K. Nanchahal, and N.J. Wald: Relation of urinary cotinine concentrations to cigarette smoking and to exposure to other people's smoke; Thorax 45 (1990) 356–361.
322. Boswell, C., M. Curvall, R.K. Elswick Jr. and D. Leyden: Modelling nicotine intake in smokers and snuff users using biological fluid nicotine metabolites; Biomarkers 5 (2000) 341–354.
323. Schepers, G. and D. Demetriou: Determination of nicotine and its metabolites in urine by HPLC after DETBA derivatization; 8th Annual Society for Research and Tobacco Conference 20–23rd February 2002, Savannah, Georgia, US.
324. Schulte-Hobein, B., D. Schwartz-Bickenbach, S. Abt, C. Plum, and H. Nau: Cigarette smoke exposure and development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant's urine; Acta Paediatr. 81 (1992) 550–557.
325. Schwartz-Bickenbach, D., B. Schulte-Hobein, S. Abt, C. Plum, and H. Nau: Smoking and passive smoking during pregnancy and early infancy: effects on birth weight, lactation period and cotinine concentrations in mother's milk and infant's urine; Toxicol. Lett. 35 (1987) 73–81.
326. Kintz, P. and P. Mangin: Determination of gestational opiate, nicotine, benzodiazepine, cocaine and ampheta-mine exposure by hair analysis; J. Forensic Sci. Soc. 33 (1993) 139–142.
327. Uematsu, T.: Therapeutic drug monitoring in hair samples; Clin. Pharmacokinet. 25 (1993) 83–87.
328. Al-Delaimy, W.K.: Hair as a biomarker for exposure to tobacco smoke; Tobacco Control 11 (2002) 176–182.
329. Pichini, S., I. Altieri, M. Pellegrini, R. Pacifici, and P. Zuccaro: Hair analysis for nicotine and cotinine: evaluation of extraction procedures, hair treatments and development of reference material; Forensic Sci. Int. 84 (1997) 243–252.
330. Kintz, P.: Gas chromatographic analysis of nicotine and cotinine in hair; J. Chrom. 580 (1992) 347–353.
331. Mizuno, A., T. Uematsu, A. Oshima, M. Nakamura, and M. Nakashima: Analysis of nicotine content of hair for assessing individual cigarette-smoking behaviour; Ther. Drug Monit. 15 (1993) 99–104.
332. Nilsen, T. and O.G. Nilsen: Accumulation of nicotine in human hair during long-term controlled exposure to a low concentration of nicotine vapour; Pharmacol. Toxicol. 81 (1997) 48–52.
333. Zahlsen, K. and O.G. Nilsen: Gas chromatographic analysis of nicotine in hair; Environ. Technol. 11 (1990) 353–364.
334. Dimish-Ward, H., H. Gee, M. Brauer, and V. Leung: Analysis of nicotine and cotinine in the hair of hospitality workers exposed to environmental tobacco smoke; J. Occ. Environ. Med. 39 (1997) 946–948.
335. Gerstenberg, B., G. Schepers, P. Voncken, and H. Völkel: Nicotine and cotinine accumulation in pigmented and unpigmented rat hair; Drug Metab. Dispos. 23 (1995) 143–148.
336. Dehn, D.L., D.J. Claffey, M.W. Duncan, and J.A. Ruth: Nicotine and cotinine adducts of a melanin intermediate demonstrated by matrix-assisted laser desorption/ioni-zation time-of-flight mas spectrometry; Chem. Res. Toxicol. 14 (2001) 275–279.
337. C. Eliopoulos, J. Klein, and G. Koren: Validation of self-reported smoking by analysis of hair for nicotine and cotinine; Ther. Drug Monitor. 18 (1996) 532–536.
338. Uematsu, T., A. Mizuno, S. Nagashima, A. Oshima, and M. Nakamura: The axial distribution of nicotine content along hair shaft as an indicator of changes in smoking behaviour: elevation in a smoking-cessation programme with or without the aid of nicotine chewing gum; Br. J. clin. Pharmac. 39 (1995) 665–669.
339. Pichini, S., Ó. Garcia-Algar, L. Munoz, O. Vall, R. Pacifici, C. Figueroa, J.A. Pascual, D. Diaz, and J. Sunyer: Assessment of chronic exposure to cigarette smoke and its change during pregnancy by segmental hair analysis; J. Exposure Anal. Environ. Epidemiol. 13 (2003) 144–151.
340. Feldman, Y., G. Koren, D. Mattice, H. Shear, E. Pellegrini, and S.M. MacLeod: Determinants of recall and recall bias in studying drug and chemical exposures in pregnancy; Teratology 49 (1989) 37–45.
341. Kintz, P., B. Ludes, and P. Mangin: Evaluation of nicotine and cotinine in human hair; J. Forensic Sci. 37 (1992) 72–76.
342. Klein, J. and G. Koren: Hair analysis – a biological marker for passive smoking in pregnancy and childhood; Human Expt. Toxicol. 18 (1999) 279–282.
343. Hardee, G.E., T. Stewart, and A.C. Capomacchia: Tobacco smoke xenobiotic compound appearance in mother's milk and involuntary smoke exposures. I. Nicotine and cotinine; Toxicol. Lett. 15 (1983) 109–112.
344. Luck, W. and H. Nau: Nicotine and cotinine concen-trations in the milk of smoking mothers: influence of cigarette consumption and diurnal variation; Eur. J. Pediatr. 146 (1987) 21–26.
345. Schiffman, M.H., N.J. Haley., J.S. Felton, A.W. Andrews, R.A. Kaslow, W.D. Lancaster, R.J. Kurman, L.A. Brinton, L.B. Lannom, and D. Hoffmann: Biochemical epidemiology of cervical neoplasia: measuring cigarette smoke constituents in the cervix; Cancer Res. 44 (1987) 3886–3888.
346. Jones, C.J., M.H. Schiffman, R. Kurman, P. Jacob III., and N.L. Benowitz: Elevated nicotine levels in cervical lavages from passive smokers; J. Publ. Health 81 (1991) 378–379.
347. McCann, M.F., D.E. Irwin, L.A. Walton, B.S. Hulka, J.L. Morton, and C.M. Axelrad: Nicotine and cotinine in the cervical mucus of smokers, passive smokers and nonsmokers; Cancer Epidemiol. Biomarkers Prev. 1 (1992) 125–129.
348. Poppe, W.A., R. Peeters, P. Daenens, P.S. Ide, and F.A. Van Assche: Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical fluid; Gynecol. Obstet. Invest. 39 (1995) 110–114.
349. Vine, M.F., C.J. Tse, P. Hu, and K.Y. Truong: Cigarette smoking and semen quality; Fertil. Steril. 65 (1996) 835–842.
350. Macaron, C.I., Z. Macaron, M.-T. Maalouf, and G. Khazaal: Cotinine in seminal fluids of smokers, passive smokers and nonsmokers; J. Med. Liban. 45 (1997) 46.
351. Balabanova, S., G. Bühler, E. Schneider, H.J. Boschek, and H. Schneiter: Über die Ausscheidung von Nikotin mit dem apokrinen und ekkrinen Schweiß bei Rauchern und Passiv-Rauchern [Nicotine excretion by the apo-crine and eccrine sweat in smokers and passive smokers]; Hautarzt 43 (1992) 73–76.
352. Kintz, P., A. Henrich, V. Cirimele, and B. Ludes: Nicotine monitoring in sweat with a sweat patch; J. Chromatogr. B 705 (1998) 357–361.
353. Al-Delaimy, W.K., G.N. Mahoney, F.E. Speizer, and W.C. Willett: Toenail nicotine levels as a biomarker of tobacco smoke exposure; Cancer Epidemiol. Bio-markers & Prev. 11 (2002) 1400–1404.
354. Garcia-Algar, Ó., O. Vall, J. Segura, J.A. Pascual, D. Diaz, L. Muñoz, P. Zuccaro, R. Pacifici, and S. Pichini: Nicotine concentrations in deciduous teeth and cumu-lative exposure to tobacco smoke during childhood; JAMA 290 (2003) 196–197.
355. Fukami, T., M. Nakajima, R. Yoshida, Y. Tsuchiya, Y. Fujiki, M. Katoh, H.L. MeLeod, and T. Yokoi: A novel polymorphism of human CYP2A6 gene CYP2A6*17 has an amino acid substitution (V365M) that decreases enzyme activity in vitro and in vivo; Clin. Pharmacol. Ther. 76 (2004) 519–527.
356. Jarvis, M.J., C. Feyerabend, A. Bryant, B. Hedges, and P. Primatesta: Passive smoking in the home: plasma cotinine concentrations in non-smokers with smoking partners; Tobacco Control 10 (2001) 368–374.
357. Martínez, M.E., M. Reid, R. Jiang, J. Einspahr, and D.S. Alberts: Accuracy of self-reported smoking status among participants in a chemoprevention trial; Prev. Med. 38 (2004) 492–497.
358. Goulay, S.G., N.L. Benowitz, A. Forbes, and J.J. McNeill: Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine replacement; Eur. J. Clin. Pharmacol. 51 (1997) 407–414.
359. Li, C.Q., R.A. Windsor, L. Perkins, R.L. Goldenberg, and J.B. Lowe: The impact on infant birthweight and gestational age of cotinine-validated smoking reduction during pregnancy; JAMA 269 (1993) 1519–1524.