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.
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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 13-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.