title: Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.
abstract: There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a "fit for purpose" approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid - did not reproducibly discriminate smokers and non-smokers. Furthermore, there are currently no agreed common reference standards to measure absolute concentrations and few inter-laboratory trials have been performed to establish consensus values for interim standards. Thus, we also discuss in this review additional requirements for the generation of robust data on urinary biomarkers, including toxicant metabolism and disposition, method validation and qualification for use in tobacco products comparison studies.
authors.affiliation: ENI Limited , Towcester , United Kingdom and.
authors.forename: Evan O
authors.initials: EO
authors.lastname: Gregg
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Minet
authors.forename: Michael
authors.initials: M
authors.lastname: McEwan
mesh_terms: D015415:Biomarkers / Q000652:urine*; D006801:Humans; D012907:Smoking / Q000652:urine*; D062789:Tobacco Products
chemical_list: D015415:Biomarkers
references.citation: J Occup Health. 2007 Mar;49(2):140-51
references.pmid: 17429172
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 1;878(27):2520-8
references.pmid: 20227354
references.citation: Chem Biol Interact. 2010 Mar 19;184(1-2):182-8
references.pmid: 20026093
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Aug;10(8):883-8
references.pmid: 11489755
references.citation: Regul Toxicol Pharmacol. 2008 Nov;52(2):111-7
references.pmid: 18619511
references.citation: J Chromatogr B Biomed Sci Appl. 1998 Oct 9;717(1-2):179-99
references.pmid: 9832246
references.citation: Chem Res Toxicol. 2011 Sep 19;24(9):1516-26
references.pmid: 21749114
references.citation: J Clin Pharmacol. 2008 May;48(5):580-91
references.pmid: 18319361
references.citation: Nicotine Tob Res. 2006 Apr;8(2):169-91
references.pmid: 16766411
references.citation: Proc Natl Acad Sci U S A. 1988 Dec;85(24):9788-91
references.pmid: 3200858
references.citation: Int J Hyg Environ Health. 2007 May;210(3-4):201-28
references.pmid: 17376741
references.citation: Drug Metab Dispos. 2002 Apr;30(4):397-403
references.pmid: 11901093
references.citation: Drug Metab Dispos. 2001 Aug;29(8):1096-101
references.pmid: 11454727
references.citation: Cancer Res. 2011 Nov 1;71(21):6749-57
references.pmid: 22028322
references.citation: Biomarkers. 2011 Feb;16(1):89-96
references.pmid: 21108560
references.citation: Physiol Rev. 1959 Jul;39(3):577-616
references.pmid: 13674905
references.citation: Tob Control. 2013 May;22(3):164-71
references.pmid: 22940677
references.citation: Int Arch Occup Environ Health. 1998 Oct;71(7):499-502
references.pmid: 9826084
references.citation: Nicotine Tob Res. 2005 Oct;7(5):729-38
references.pmid: 16191744
references.citation: Psychopharmacology (Berl). 1992;106(3):421-7
references.pmid: 1570391
references.citation: Toxicol Lett. 2008 Nov 10;182(1-3):7-17
references.pmid: 18848868
references.citation: BMJ. 2008 May 3;336(7651):1003-6
references.pmid: 18403498
references.citation: Regul Toxicol Pharmacol. 2008 Nov;52(2):104-10
references.pmid: 18640172
references.citation: Carcinogenesis. 1992 Jun;13(6):955-61
references.pmid: 1600616
references.citation: Mutat Res. 1996 Sep 26;361(1):1-9
references.pmid: 8816936
references.citation: Chem Res Toxicol. 2011 Jan 14;24(1):119-24
references.pmid: 21090699
references.citation: Regul Toxicol Pharmacol. 2007 Mar;47(2):171-83
references.pmid: 17034917
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Apr 15;877(11-12):1185-92
references.pmid: 19328751
references.citation: Drug Metab Dispos. 2004 Sep;32(9):915-22
references.pmid: 15319331
references.citation: Chem Res Toxicol. 1993 Nov-Dec;6(6):866-71
references.pmid: 8117926
references.citation: Toxicol Appl Pharmacol. 2010 Sep 15;247(3):198-203
references.pmid: 20637790
references.citation: Br Med J. 1976 Jun 12;1(6023):1430-3
references.pmid: 953530
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Oct 25;796(1):131-40
references.pmid: 14552824
references.citation: Toxicol Lett. 2010 Apr 1;193(3):229-35
references.pmid: 20100551
references.citation: Drug Metab Dispos. 2005 Feb;33(2):258-61
references.pmid: 15528319
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):884-93
references.pmid: 19258471
references.citation: Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):937-45
references.pmid: 23539508
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1480-4
references.pmid: 8108434
references.citation: J Clin Pharmacol. 2007 Apr;47(4):518-30
references.pmid: 17389561
references.citation: Toxicol Lett. 1998 Mar 31;95(2):123-9
references.pmid: 9635416
references.citation: Anal Chem. 2005 Dec 1;77(23):7639-45
references.pmid: 16316171
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1082-90
references.pmid: 12376511
references.citation: Alcohol Alcohol Suppl. 1994;2:141-5
references.pmid: 8974328
references.citation: J Anal Toxicol. 2006 Apr;30(3):187-95
references.pmid: 16803653
references.citation: Toxicol Lett. 2006 Apr 10;162(2-3):181-5
references.pmid: 16406420
references.citation: Drug Metab Dispos. 2002 Jan;30(1):69-73
references.pmid: 11744614
references.citation: Chem Res Toxicol. 2009 Jun;22(6):1018-25
references.pmid: 19522547
references.citation: Chem Res Toxicol. 2010 Jun 21;23(6):1001-8
references.pmid: 20408564
references.citation: Scand J Work Environ Health. 1986 Apr;12(2):137-43
references.pmid: 3726495
references.citation: Cancer Res. 1999 Feb 1;59(3):590-6
references.pmid: 9973205
references.citation: Drug Metab Dispos. 2002 Aug;30(8):911-7
references.pmid: 12124309
references.citation: Crit Rev Toxicol. 1992;22(5-6):271-306
references.pmid: 1489508
references.citation: J Chromatogr B Biomed Appl. 1995 Apr 7;666(1):71-6
references.pmid: 7655623
references.citation: Chem Res Toxicol. 2009 Apr;22(4):734-41
references.pmid: 19317515
references.citation: Carcinogenesis. 2006 Apr;27(4):772-81
references.pmid: 16339183
references.citation: J Clin Hypertens (Greenwich). 2010 Mar;12(3):174-80
references.pmid: 20433530
references.citation: IARC Sci Publ. 1980;(31):349-59
references.pmid: 7228264
references.citation: Anal Chem. 1997 Oct 1;69(19):3930-9
references.pmid: 9322431
references.citation: Inhal Toxicol. 2006 Sep;18(10):821-9
references.pmid: 16774872
references.citation: Int J Cancer. 1996 Jan 26;65(3):314-6
references.pmid: 8575850
references.citation: Pharmacogenet Genomics. 2011 Feb;21(2):55-65
references.pmid: 21164388
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Oct 5;778(1-2):179-92
references.pmid: 12376125
references.citation: Cancer Res. 2009 Apr 1;69(7):2990-5
references.pmid: 19318550
references.citation: Biomarkers. 2000;5(1):33-45
references.pmid: 23885904
references.citation: Biomarkers. 2006 Jan-Feb;11(1):28-52
references.pmid: 16484135
references.citation: Exp Toxicol Pathol. 2005 Jul;57 Suppl 1:75-110
references.pmid: 16092718
references.citation: J Pharm Biomed Anal. 2006 Mar 3;40(4):928-42
references.pmid: 16182503
references.citation: Hum Exp Toxicol. 2007 Jan;26(1):37-47
references.pmid: 17334178
references.citation: Toxicol Lett. 2012 Aug 13;213(1):57-62
references.pmid: 21300142
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3421-5
references.pmid: 19959691
references.citation: Chem Res Toxicol. 1999 Jul;12(7):623-9
references.pmid: 10409402
references.citation: Tob Control. 2008 Apr;17(2):132-41
references.pmid: 18375736
references.citation: J Natl Cancer Inst. 2004 Jan 21;96(2):107-15
references.pmid: 14734700
references.citation: Anal Bioanal Chem. 2006 Dec;386(7-8):1985-93
references.pmid: 17068671
references.citation: World Health Organ Tech Rep Ser. 2008;(951):1-277, 1 p following 277
references.pmid: 19522165
references.citation: Drug Metab Dispos. 2004 Jan;32(1):72-9
references.pmid: 14709623
references.citation: Chem Res Toxicol. 2005 Jan;18(1):61-9
references.pmid: 15651850
references.citation: Miner Electrolyte Metab. 1993;19(6):385-8
references.pmid: 8164621
references.citation: Hum Exp Toxicol. 1997 Aug;16(8):449-59
references.pmid: 9292285
references.citation: Chem Res Toxicol. 2012 Apr 16;25(4):952-64
references.pmid: 22428611
references.citation: Chem Res Toxicol. 2013 Jan 18;26(1):37-45
references.pmid: 23252610
references.citation: Carcinogenesis. 1998 Oct;19(10):1847-53
references.pmid: 9806168
references.citation: Regul Toxicol Pharmacol. 2009 Oct;55(1):97-109
references.pmid: 19539004
references.citation: Cancer Res. 1995 Nov 15;55(22):5230-7
references.pmid: 7585581
references.citation: Nicotine Tob Res. 2008 Dec;10(12):1761-72
references.pmid: 19023827
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):885-91
references.pmid: 15824160
references.citation: Nicotine Tob Res. 2003 Jun;5(3):387-96
references.pmid: 12791522
references.citation: Anal Bioanal Chem. 2009 Feb;393(3):969-81
references.pmid: 19018522
references.citation: Toxicol Sci. 2005 May;85(1):624-31
references.pmid: 15716486
references.citation: Drug Metab Dispos. 2002 Oct;30(10):1115-22
references.pmid: 12228188
references.citation: Toxicol Lett. 1987 Jan;35(1):45-52
references.pmid: 3810681
references.citation: Int J Mol Epidemiol Genet. 2010 Aug 05;1(4):295-309
references.pmid: 21532841
references.citation: Food Chem Toxicol. 1990 Sep;28(9):639-46
references.pmid: 2272562
references.citation: Toxicol Appl Pharmacol. 2011 Jun 1;253(2):145-52
references.pmid: 21473878
references.citation: Clin Cancer Res. 2008 Oct 1;14(19):5967-76
references.pmid: 18829475
references.citation: J Agric Food Chem. 2002 Aug 14;50(17):4998-5006
references.pmid: 12166997
references.citation: J Natl Cancer Inst. 1990 Dec 5;82(23):1826-31
references.pmid: 2250298
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2969-77
references.pmid: 20833972
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Dec;12(12):1544-6
references.pmid: 14693752
references.citation: Toxicol Lett. 2011 Jun 10;203(2):118-26
references.pmid: 21402133
references.citation: Cancer Res. 2009 Sep 15;69(18):7170-4
references.pmid: 19738046
references.citation: J Chromatogr B Biomed Sci Appl. 2001 Jan 5;750(1):163-9
references.pmid: 11204217
references.citation: Nutr Metab Cardiovasc Dis. 2000 Apr;10(2):85-91
references.pmid: 10919173
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):796-802
references.pmid: 17416773
references.citation: Environ Health Perspect. 1994 Nov;102 Suppl 9:55-61
references.pmid: 7698086
references.citation: Anal Biochem. 2004 Apr 15;327(2):184-99
references.pmid: 15051535
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):266-71
references.pmid: 16492914
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):260-6
references.pmid: 19124507
references.citation: Toxicology. 1996 Oct 28;113(1-3):306-9
references.pmid: 8901914
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2009 May 15;877(14-15):1575-82
references.pmid: 19395323
references.citation: IARC Sci Publ. 2001;154:245-55
references.pmid: 11220664
references.citation: Toxicol Lett. 2002 Mar 10;128(1-3):249-55
references.pmid: 11869835
references.citation: Arch Biochem Biophys. 2007 Aug 15;464(2):169-75
references.pmid: 17601487
references.citation: Cancer Lett. 2000 Jun 1;154(1):39-43
references.pmid: 10799737
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Jul;13(7):1261-4
references.pmid: 15247141
references.citation: Cancer Res. 1998 Feb 15;58(4):581-4
references.pmid: 9485001
references.citation: J Clin Pharmacol. 2005 Feb;45(2):133-45
references.pmid: 15647405
references.citation: Sci Total Environ. 2007 Sep 1;382(2-3):214-23
references.pmid: 17544058
references.citation: Int J Cancer. 2012 Mar 15;130(6):1338-46
references.pmid: 21544809
references.citation: Chem Res Toxicol. 2007 Jul;20(7):986-90
references.pmid: 17559234
references.citation: Toxicol Lett. 2010 Mar 1;193(1):1-3
references.pmid: 19963048
references.citation: Biomarkers. 2011 May;16(3):212-21
references.pmid: 21438718
references.citation: Psychopharmacology (Berl). 1999 Jul;145(1):1-20
references.pmid: 10445368
references.citation: Arch Environ Contam Toxicol. 2000 Apr;38(3):377-83
references.pmid: 10667937
references.citation: Br J Addict. 1992 Jan;87(1):111-3
references.pmid: 1543931
references.citation: J Am Chem Soc. 2009 Mar 18;131(10):3414-5
references.pmid: 19239220
references.citation: Chem Res Toxicol. 2000 Nov;13(11):1149-57
references.pmid: 11087437
references.citation: J Expo Anal Environ Epidemiol. 2000 Mar-Apr;10(2):126-35
references.pmid: 10791594
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6115-20
references.pmid: 18420820
references.citation: Cancer Res. 2011 Apr 1;71(7):2572-81
references.pmid: 21325429
references.citation: Cancer Epidemiol Biomarkers Prev. 1997 Feb;6(2):113-20
references.pmid: 9037562
references.citation: Mutat Res. 2001 Oct 1;482(1-2):41-6
references.pmid: 11535247
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Apr;9(4):373-80
references.pmid: 10794481
references.citation: Biomarkers. 2010 Jun;15(4):345-52
references.pmid: 20374068
references.citation: Carcinogenesis. 2012 Apr;33(4):804-9
references.pmid: 22298640
references.citation: Sci Total Environ. 2000 Feb 28;247(1):81-90
references.pmid: 10721145
references.citation: Regul Toxicol Pharmacol. 2006 Apr;44(3):262-7
references.pmid: 16442193
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):433-43
references.pmid: 19190172
references.citation: Nicotine Tob Res. 2012 Jan;14(1):29-42
references.pmid: 21330282
references.citation: Arch Toxicol. 2010 Jun;84(6):461-9
references.pmid: 20127315
references.citation: J Biol Chem. 2001 Jul 27;276(30):27846-54
references.pmid: 11375986
references.citation: Pharm Res. 2006 Feb;23(2):312-28
references.pmid: 16397743
references.citation: Carcinogenesis. 1999 Sep;20(9):1825-30
references.pmid: 10469630
references.citation: Toxicol Sci. 2000 Jul;56(1):189-202
references.pmid: 10869468
references.citation: Chem Res Toxicol. 2002 Apr;15(4):545-50
references.pmid: 11952341
references.citation: BMC Res Notes. 2011 Oct 10;4:391
references.pmid: 21985092
references.citation: Drug Metab Dispos. 2010 Oct;38(10):1679-87
references.pmid: 20616185
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Aug;13(8):1342-8
references.pmid: 15298956
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1119-22
references.pmid: 11045797
references.citation: J Toxicol Environ Health A. 2007 Oct;70(20):1779-82
references.pmid: 17885936
references.citation: Thorax. 1981 May;36(5):366-9
references.pmid: 7314006
references.citation: Toxicol Appl Pharmacol. 2006 Jun 15;213(3):198-206
references.pmid: 16405939
references.citation: Addiction. 2013 Mar;108(3):607-17
references.pmid: 22971134
references.citation: Free Radic Biol Med. 1991;11(1):81-128
references.pmid: 1937131
references.citation: Pharmacogenet Genomics. 2005 Nov;15(11):769-78
references.pmid: 16220109
references.citation: Chem Res Toxicol. 2007 Jan;20(1):108-13
references.pmid: 17226933
references.citation: Toxicology. 2008 Mar 12;245(1-2):154-61
references.pmid: 18243467
references.citation: Inhal Toxicol. 2006 Sep;18(10):831-9
references.pmid: 16774873
references.citation: Nicotine Tob Res. 2010 Feb;12(2):105-16
references.pmid: 20026503
references.citation: Carcinogenesis. 1995 Oct;16(10):2287-93
references.pmid: 7586124
references.citation: Environ Mol Mutagen. 1991;17(4):244-52
references.pmid: 2050132
references.citation: Carcinogenesis. 1997 Aug;18(8):1623-30
references.pmid: 9276639
references.citation: Int J Hyg Environ Health. 2011 Jun;214(3):196-204
references.pmid: 21459667
references.citation: Mutat Res. 2011 Feb 3;719(1-2):7-13
references.pmid: 20951227
references.citation: Forensic Sci Int. 2009 Apr 15;186(1-3):48-51
references.pmid: 19216038
references.citation: J Appl Toxicol. 2006 Nov-Dec;26(6):524-32
references.pmid: 17080401
references.citation: Carcinogenesis. 1996 Oct;17(10):2105-11
references.pmid: 8895475
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1524-36
references.pmid: 21613391
references.citation: Int Arch Occup Environ Health. 2011 Mar;84(3):303-13
references.pmid: 20596721
references.citation: Biomarkers. 2009 Dec;14(8):547-53
references.pmid: 19747086
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Jul;9(7):705-12
references.pmid: 10919741
references.citation: Pharmacogenetics. 1999 Aug;9(4):445-51
references.pmid: 10780264
references.citation: Chem Res Toxicol. 2012 Aug 20;25(8):1565-7
references.pmid: 22817647
references.citation: Drug Metab Dispos. 2006 Mar;34(3):464-70
references.pmid: 16381663
references.citation: Pharmacogenetics. 2001 Dec;11(9):815-24
references.pmid: 11740346
references.citation: Rapid Commun Mass Spectrom. 2011 Jan 15;25(1):115-21
references.pmid: 21154658
references.citation: Cancer Sci. 2004 Jan;95(1):1-6
references.pmid: 14720319
references.citation: J Pharmacol Exp Ther. 2005 Dec;315(3):1143-9
references.pmid: 16120810