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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-02-26 21:22:53 UTC
HMDB IDHMDB0001046
Secondary Accession Numbers
  • HMDB01046
Metabolite Identification
Common NameCotinine
DescriptionCotinine, also known as (S)-cotinine or cotininum, belongs to the class of organic compounds known as pyrrolidinylpyridines. Pyrrolidinylpyridines are compounds containing a pyrrolidinylpyridine ring system, which consists of a pyrrolidine ring linked to a pyridine ring. The first is mediated by a cytochrome P450 system (mainly CYP2A6 and CYP2B6) to produce nicotine iminium ion. Cotinine is a strong basic compound (based on its pKa). Within humans, cotinine participates in a number of enzymatic reactions. In particular, cotinine can be biosynthesized from nicotine imine through the action of the enzyme aldehyde oxidase. In addition, cotinine can be converted into hydroxycotinine through the action of the enzyme cytochrome P450 2A6. Indeed, it appears that most of the reported urinary metabolites of nicotine are derived from cotinine. The second step is catalyzed by aldehyde oxidase (AOX). In humans, cotinine is involved in nicotine action pathway. Quantitatively, the most important metabolite of nicotine in most mammalian species is cotinine. Outside of the human body, Cotinine has been detected, but not quantified in, several different foods, such as medlars, arrowhead, lotus, alaska blueberries, and thistles. This could make cotinine a potential biomarker for the consumption of these foods. It has demonstrated nootropic and antipsychotic-like effects in animal models. Cotinine is a potentially toxic compound.
Structure
Data?1582752173
Synonyms
ValueSource
Cotinine(15% OF the dose)HMDB
(-)-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 KeyUIKROCXWUNQSPJ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrrolidinylpyridines. Pyrrolidinylpyridines 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
Substituents
  • 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
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

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 g/LALOGPS
logP0.39ALOGPS
logP0.21ChemAxon
logS-0.18ALOGPS
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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-9500000000-f031a7d223ea527c7a80Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-004i-0900000000-61e8e1349a9d42866260Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-9500000000-f031a7d223ea527c7a80Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-004i-0900000000-61e8e1349a9d42866260Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0gdl-6900000000-7eb4053aab6127e95391Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-2900000000-7f61a2f6f72860e4c6e1Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9100000000-3a5b30b90a390122b868Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-b82772b6f28d39966cd1Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-60) , Positivesplash10-0002-9500000000-e8a00bc1cf980c18ed06Spectrum
LC-MS/MSLC-MS/MS Spectrum - CI-B (HITACHI M-60) , Positivesplash10-004i-0900000000-61e8e1349a9d42866260Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-16fb662f236943b7061eSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0900000000-bb6734f53ed607f8551fSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-3900000000-b7fe72bb7584aa19a736Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-2900000000-bb9334268373122b4f81Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0900000000-a4a59884dbcf842f195aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1900000000-0cfe8e8d340c82c8fd11Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0k9y-9500000000-e18e0cea3d758c6ff768Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-6fcf3e50bea7e8c25008Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0900000000-dad0516bb0862355ae61Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05r4-9700000000-36486e0d1769fb592c7aSpectrum
MSMass Spectrum (Electron Ionization)splash10-002b-9600000000-0cc3afdaebb529092e24Spectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Locations
  • Adipose Tissue
  • Brain
  • Cervical
  • Hair
  • Kidney
  • Liver
  • Placenta
  • Platelet
  • Testes
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
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
BiospecimenStatusValueAgeSexConditionReferenceDetails
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. [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 IDNot Available
BiGG IDNot Available
Wikipedia LinkCotinine
METLIN ID1531
PubChem Compound408
PDB IDNot Available
ChEBI ID127762
Food Biomarker OntologyNot Available
VMH IDNot Available
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. [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 ]

Enzymes

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