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Showing metabocard for Cotinine (HMDB0001046)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (1) Show 1 proteinXML
enzymes (1) Show 1 protein
Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2023-02-21 17:15:24 UTC
HMDB IDHMDB0001046
Secondary Accession Numbers
  • HMDB01046
Metabolite Identification
Common NameCotinine
DescriptionCotinine is an alkaloid found in tobacco (Nicotiana tabacum). Cotinine 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. It is also the predominant human metabolite of nicotine (when nicotine is inhaled or absorbed). In humans, about 70 to 80% of nicotine that is inhaled or absorbed 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 is widely used as a biomarker for exposure to tobacco smoke. Cotinine has an in vivo half-life of approximately 20 hours, and is typically detectable for several days (up to one week) after the use of tobacco. Similar to nicotine, cotinine binds to, activates, and desensitizes neuronal nicotinic acetylcholine receptors, though at much lower potency in comparison. It has demonstrated nootropic and antipsychotic-like effects in animal models. Cotinine treatment has also been shown to reduce depression, anxiety, and fear-related behavior as well as memory impairment in animal models of depression, PTSD, and Alzheimer's disease.
Structure
Data?1676999724
MOLSDFPDBSMILESInChI

MOL for HMDB0001046 (Cotinine)

Not Available

3D MOL for HMDB0001046 (Cotinine)

Not Available

3D SDF for HMDB0001046 (Cotinine)

Not Available

3D-SDF for HMDB0001046 (Cotinine)

Not Available

PDB for HMDB0001046 (Cotinine)

Not Available

3D PDB for HMDB0001046 (Cotinine)

Not Available

SMILES for HMDB0001046 (Cotinine)

Not Available

INCHI for HMDB0001046 (Cotinine)

Not Available
View in JSmolView NMR AssignmentsView Stereo Labels
SynonymsNot Available
Chemical FormulaC10H12N2O
Average Molecular Weight176.2151
Monoisotopic Molecular Weight176.094963016
IUPAC NameNot Available
Traditional NameNot Available
CAS Registry Number486-56-6
SMILESNot Available
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
ClassificationNot classified
Ontology
Not AvailableNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point41 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP0.07LI,NY & GORROD,JW (1992)
Experimental Chromatographic Properties
Predicted Molecular PropertiesNot Available
Predicted Chromatographic Properties

Predicted Retention Times

Underivatized

Chromatographic MethodRetention TimeReference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.2.93 minutes32390414
Predicted by Siyang on May 30, 20228.5823 minutes33406817
Predicted by Siyang using ReTip algorithm on June 8, 20221.66 minutes32390414
AjsUoB = Accucore 150 Amide HILIC with 10mM Ammonium Formate, 0.1% Formic Acid68.1 seconds40023050
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid693.8 seconds40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid252.9 seconds40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid91.2 seconds40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid159.5 seconds40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid43.5 seconds40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid226.5 seconds40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid262.9 seconds40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)153.9 seconds40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid589.8 seconds40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid39.8 seconds40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid748.0 seconds40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid170.3 seconds40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid173.4 seconds40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate484.0 seconds40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA415.4 seconds40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water156.0 seconds40023050

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
CotinineCN1C(CCC1=O)C1=CN=CC=C12407.1Standard polar33892256
CotinineCN1C(CCC1=O)C1=CN=CC=C11630.9Standard non polar33892256
CotinineCN1C(CCC1=O)C1=CN=CC=C11726.5Semi standard non polar33892256
Spectra
Biological Properties
Cellular Locations
  • Cytoplasm
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Locations
  • Adipose Tissue
  • Brain
  • Hair
  • Kidney
  • Liver
  • Placenta
  • Platelet
  • Testis
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified1.4 +/- 0.9 uMAdult (>18 years old)BothNormal details
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 but not QuantifiedNot QuantifiedAdult (>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
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified2.5 (1.13-4.54) uMAdult (>18 years old)BothActive tobacco user details
BloodDetected and Quantified2.15 (0.11-25.00) uMAdult (>18 years old)BothSmoking 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 Quantified1.6 (0.37-3.0) umol/mmol creatinineAdult (>18 years old)BothActive tobacco user details
UrineDetected and Quantified0.32 (0.0022-1.47) umol/mmol creatinineAdult (>18 years old)BothSmoking 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
External LinksNot 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

Enzyme Details
1. Aldehyde oxidase
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular weight:
147916.735