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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:45 UTC
HMDB IDHMDB01046
Secondary Accession NumbersNone
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.
Structure
Thumb
Synonyms
ValueSource
Cotinine(15% OF the dose)ChEMBL
(-)-CotinineHMDB
(S)-(-)-CotinineHMDB
(S)-CotinineHMDB
CotininaHMDB
CotininumHMDB
S-(-)-CotinineHMDB
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
SMILES
CN1C(CCC1=O)C1=CN=CC=C1
InChI Identifier
InChI=1S/C10H12N2O/c1-12-9(4-5-10(12)13)8-3-2-6-11-7-8/h2-3,6-7,9H,4-5H2,1H3
InChI KeyInChIKey=UIKROCXWUNQSPJ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassNot Available
Sub ClassNot Available
Direct ParentAlkaloids and derivatives
Alternative Parents
Substituents
  • Nicotine
  • Alkaloid or derivatives
  • Pyrrolidinylpyridine
  • N-alkylpyrrolidine
  • 2-pyrrolidone
  • Pyrrolidone
  • Pyridine
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug metabolite
Biofunction
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point41 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP0.07LI,NY & GORROD,JW (1992)
Predicted Properties
PropertyValueSource
Water Solubility117.0 mg/mLALOGPS
logP0.39ALOGPS
logP0.21ChemAxon
logS-0.18ALOGPS
pKa (Strongest Basic)4.79ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area33.2 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity49.28 m3·mol-1ChemAxon
Polarizability18.57 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
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
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 Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
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
Pathways
NameSMPDB LinkKEGG Link
Nicotine Metabolism PathwaySMP00628Not Available
Nicotine PathwaySMP00431Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000284 (0.000267-0.000426) uMChildren (1-13 years old)Not SpecifiedNormal
    • National Health a...
details
BloodDetected and Quantified0.000261 (0.000238-0.000289) uMAdult (>18 years old)Not SpecifiedNormal
    • National Health a...
details
BloodDetected and Quantified0.00908 (0.00675-0.0135) uMAdult (>18 years old)Not SpecifiedNormal
    • National Health a...
details
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
BiofluidStatusValueAgeSexConditionReferenceDetails
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
Smoking
  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. [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. [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. Epub 2008 Oct 15. [19036546 ]
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00519
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB004716
KNApSAcK IDC00034470
Chemspider ID395
KEGG Compound IDNot Available
BioCyc IDCPD-2742
BiGG IDNot Available
Wikipedia LinkCotinine
NuGOwiki LinkHMDB01046
Metagene LinkHMDB01046
METLIN ID1531
PubChem Compound408
PDB IDNot Available
ChEBI ID127762
References
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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [16521941 ]
  11. Nicotine absorption by workers harvesting green tobacco. Lancet. 1975 Mar 1;1(7905):478-80. [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. [12608620 ]
  13. Paszkowski T: [Concentration gradient of cotinine between blood serum and preovulatory follicular fluid] Ginekol Pol. 1998 Dec;69(12):1131-6. [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. [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. [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. [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. [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. [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. [15743729 ]
  20. Kintz P: Gas chromatographic analysis of nicotine and cotinine in hair. J Chromatogr. 1992 Sep 16;580(1-2):347-53. [1400830 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular weight:
147916.735