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Record Information
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-12-20 20:31:04 UTC
Secondary Accession Numbers
  • HMDB01046
Metabolite Identification
Common NameCotinine
DescriptionQuantitatively, the most important metabolite of nicotine in most mammalian species is cotinine. In humans, about 70 to 80% of nicotine is converted to cotinine. This transformation involves two steps. The first is mediated by a cytochrome P450 system (mainly CYP2A6 and CYP2B6) to produce nicotine iminium ion. The second step is catalyzed by aldehyde oxidase (AOX). A number of cotinine metabolites have also been structurally characterized. Indeed, it appears that most of the reported urinary metabolites of nicotine are derived from cotinine.
Cotinine(15% OF the dose)ChEMBL
Chemical FormulaC10H12N2O
Average Molecular Weight176.2151
Monoisotopic Molecular Weight176.094963016
IUPAC Name1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
Traditional Name(-)-cotinine
CAS Registry Number486-56-6
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrrolidinylpyridines. These are compounds containing a pyrrolidinylpyridine ring system, which consists of a pyrrolidine ring linked to a pyridine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyrrolidinylpyridines
Direct ParentPyrrolidinylpyridines
Alternative Parents
  • Pyrrolidinylpyridine
  • Alkaloid or derivatives
  • Pyrrolidone
  • 2-pyrrolidone
  • N-alkylpyrrolidine
  • Pyrrolidine
  • Tertiary carboxylic acid amide
  • Heteroaromatic compound
  • Lactam
  • Carboxamide group
  • Carboxylic acid derivative
  • Azacycle
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Biological location:


  Biofluid and excreta:

  Tissue and substructures:

  Organ and components:

  Cell and elements:



Route of exposure:







Naturally occurring process:

  Biological process:

    Biochemical pathway:


Biological role:

Industrial application:

  Pharmaceutical industry:

Physical Properties
Experimental Properties
Melting Point41 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP0.07LI,NY & GORROD,JW (1992)
Predicted Properties
Water Solubility117 g/LALOGPS
pKa (Strongest Basic)4.79ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area33.2 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity49.28 m³·mol⁻¹ChemAxon
Polarizability18.57 ųChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-9500000000-f031a7d223ea527c7a80View in MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-004i-0900000000-61e8e1349a9d42866260View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0gdl-6900000000-7eb4053aab6127e95391View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-2900000000-7f61a2f6f72860e4c6e1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9100000000-3a5b30b90a390122b868View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-b82772b6f28d39966cd1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-60) , Positivesplash10-0002-9500000000-e8a00bc1cf980c18ed06View in MoNA
LC-MS/MSLC-MS/MS Spectrum - CI-B (HITACHI M-60) , Positivesplash10-004i-0900000000-61e8e1349a9d42866260View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-16fb662f236943b7061eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-bb6734f53ed607f8551fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-3900000000-b7fe72bb7584aa19a736View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-2900000000-bb9334268373122b4f81View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-a4a59884dbcf842f195aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1900000000-0cfe8e8d340c82c8fd11View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0k9y-9500000000-e18e0cea3d758c6ff768View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-6fcf3e50bea7e8c25008View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0900000000-dad0516bb0862355ae61View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05r4-9700000000-36486e0d1769fb592c7aView in MoNA
MSMass Spectrum (Electron Ionization)splash10-002b-9600000000-0cc3afdaebb529092e24View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Adipose Tissue
  • Brain
  • Cervical
  • Hair
  • Kidney
  • Liver
  • Placenta
  • Platelet
  • Testes
Nicotine Action PathwayThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Nicotine Metabolism PathwayThumbThumb?image type=greyscaleThumb?image type=simpleNot Available
Normal Concentrations
BloodDetected and Quantified0.000284 (0.000267-0.000426) uMChildren (1-13 years old)Not SpecifiedNormal
    • National Health a...
BloodDetected and Quantified0.000261 (0.000238-0.000289) uMAdult (>18 years old)Not SpecifiedNormal
    • National Health a...
BloodDetected and Quantified0.00908 (0.00675-0.0135) uMAdult (>18 years old)Not SpecifiedNormal
    • National Health a...
BloodDetected and Quantified1.4 +/- 0.9 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.112 +/- 0.0823 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified<1.00 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BloodDetected and Quantified2.15 (0.11-25.00) uMAdult (>18 years old)BothSmoking details
BloodDetected and Quantified2.5 (1.13-4.54) uMAdult (>18 years old)BothActive tobacco user details
Cerebrospinal Fluid (CSF)Detected and Quantified0.251 +/- 0.192 uMNewborn (0-30 days old)Not SpecifiedPassive-smokers with smoking mothers details
Cerebrospinal Fluid (CSF)Detected and Quantified0.575 +/- 0.596 uMAdult (>18 years old)Not SpecifiedSmoking details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0670 +/- 0.0664 uMChildren (1-13 years old)Not SpecifiedChildren from smoking mothers details
UrineDetected and Quantified0.32 (0.0022-1.47) umol/mmol creatinineAdult (>18 years old)BothSmoking details
UrineDetected and Quantified1.6 (0.37-3.0) umol/mmol creatinineAdult (>18 years old)BothActive tobacco user details
Associated Disorders and Diseases
Disease References
  1. Moyer TP, Charlson JR, Enger RJ, Dale LC, Ebbert JO, Schroeder DR, Hurt RD: Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem. 2002 Sep;48(9):1460-71. [PubMed:12194923 ]
  2. Massadeh AM, Gharaibeh AA, Omari KW: A single-step extraction method for the determination of nicotine and cotinine in Jordanian smokers' blood and urine samples by RP-HPLC and GC-MS. J Chromatogr Sci. 2009 Feb;47(2):170-7. [PubMed:19222926 ]
  3. Malkawi AH, Al-Ghananeem AM, de Leon J, Crooks PA: Nicotine exposure can be detected in cerebrospinal fluid of active and passive smokers. J Pharm Biomed Anal. 2009 Jan 15;49(1):129-32. doi: 10.1016/j.jpba.2008.10.003. Epub 2008 Oct 15. [PubMed:19036546 ]
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB004716
KNApSAcK IDC00034470
Chemspider ID395
KEGG Compound IDNot Available
BioCyc IDCPD-2742
BiGG IDNot Available
Wikipedia LinkCotinine
PubChem Compound408
PDB IDNot Available
ChEBI ID127762
Synthesis ReferenceRolf, David; Goon, David J. W.; Michelson, Robert H. Preparation of cotinine by reacting nicotine with bromide and bromate. U.S. (1997), 5 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Bentley MC, Abrar M, Kelk M, Cook J, Phillips K: Validation of an assay for the determination of cotinine and 3-hydroxycotinine in human saliva using automated solid-phase extraction and liquid chromatography with tandem mass spectrometric detection. J Chromatogr B Biomed Sci Appl. 1999 Feb 19;723(1-2):185-94. [PubMed:10080645 ]
  2. Urakawa N, Nagata T, Kudo K, Kimura K, Imamura T: Simultaneous determination of nicotine and cotinine in various human tissues using capillary gas chromatography/mass spectrometry. Int J Legal Med. 1994;106(5):232-6. [PubMed:8068568 ]
  3. Poppe WA, Peeters R, Drijkoningen M, Ide PS, Daenens P, Lauweryns JM, Van Assche FA: Cervical cotinine and macrophage-Langerhans cell density in the normal human uterine cervix. Gynecol Obstet Invest. 1996;41(4):253-9. [PubMed:8793496 ]
  4. Jacqz-Aigrain E, Zhang D, Maillard G, Luton D, Andre J, Oury JF: Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair. BJOG. 2002 Aug;109(8):909-11. [PubMed:12197371 ]
  5. Gwent SH, Wilson JF, Tsanaclis LM, Wicks JF: Time course of appearance of cotinine in human beard hair after a single dose of nicotine. Ther Drug Monit. 1995 Apr;17(2):195-8. [PubMed:7624910 ]
  6. Dobek D, Karmowski A, Sobiech KA, Terpilowski L, Mis-Michalek M: Average quantitative concentration of cotinine within the system pregnant woman-baby. Arch Immunol Ther Exp (Warsz). 1998;46(1):59-61. [PubMed:9510948 ]
  7. Torano JS, van Kan HJ: 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. 2003 Jul;128(7):838-43. [PubMed:12894819 ]
  8. Knight JM, Eliopoulos C, Klein J, Greenwald M, Koren G: Passive smoking in children. Racial differences in systemic exposure to cotinine by hair and urine analysis. Chest. 1996 Feb;109(2):446-50. [PubMed:8620720 ]
  9. Hatsukami DK, Jensen J, Brauer LH, Mooney M, Schulte S, Sofuoglu M, Pentel PR: Lack of effect of 5HT3 antagonist in mediating subjective and behavioral responses to cotinine. Pharmacol Biochem Behav. 2003 Apr;75(1):1-7. [PubMed:12759107 ]
  10. Laskowska-Klita T, Chelchowska M, Leibschang J: [Concentrations of cotinine in serum and urine of smoking pregnant women and in placenta and umbilical cord blood]. Przegl Lek. 2005;62(10):1007-9. [PubMed:16521941 ]
  11. Authors unspecified: Nicotine absorption by workers harvesting green tobacco. Lancet. 1975 Mar 1;1(7905):478-80. [PubMed:46956 ]
  12. Tutka P, Wielosz M, Zatonski W: Exposure to environmental tobacco smoke and children health. Int J Occup Med Environ Health. 2002;15(4):325-35. [PubMed:12608620 ]
  13. Paszkowski T: [Concentration gradient of cotinine between blood serum and preovulatory follicular fluid]. Ginekol Pol. 1998 Dec;69(12):1131-6. [PubMed:10224789 ]
  14. Poppe WA, Peeters R, Daenens P, Ide PS, Van Assche FA: Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical fluid. Gynecol Obstet Invest. 1995;39(2):110-4. [PubMed:7737579 ]
  15. Istvan JA, Lee WW, Buist AS, Connett JE: Relation of salivary cotinine to blood pressure in middle-aged cigarette smokers. Am Heart J. 1999 May;137(5):928-31. [PubMed:10220643 ]
  16. Nafstad P, Botten G, Hagen JA, Zahlsen K, Nilsen OG, Silsand T, Kongerud J: Comparison of three methods for estimating environmental tobacco smoke exposure among children aged between 12 and 36 months. Int J Epidemiol. 1995 Feb;24(1):88-94. [PubMed:7797361 ]
  17. Eliopoulos C, Klein J, Chitayat D, Greenwald M, Koren G: Nicotine and cotinine in maternal and neonatal hair as markers of gestational smoking. Clin Invest Med. 1996 Aug;19(4):231-42. [PubMed:8853571 ]
  18. Eliopoulos C, Klein J, Koren G: Validation of self-reported smoking by analysis of hair for nicotine and cotinine. Ther Drug Monit. 1996 Oct;18(5):532-6. [PubMed:8885115 ]
  19. Wilson SE, Kahn RS, Khoury J, Lanphear BP: Racial differences in exposure to environmental tobacco smoke among children. Environ Health Perspect. 2005 Mar;113(3):362-7. [PubMed:15743729 ]
  20. Kintz P: Gas chromatographic analysis of nicotine and cotinine in hair. J Chromatogr. 1992 Sep 16;580(1-2):347-53. [PubMed:1400830 ]


General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
Uniprot ID:
Molecular weight: