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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:04:33 UTC
HMDB IDHMDB01411
Secondary Accession NumbersNone
Metabolite Identification
Common NameCotinine N-oxide
DescriptionCotinine N-oxide is a minor metabolite of nicotine, cotinine formation being the major pathway of nicotine metabolism in smokers. Cotinine N-oxide accounts for less than 5% of the nicotine dose. Cotinine N-oxide can be reduced back to the parent amine in vivo. Nicotine is a naturally occurring alkaloid found in many plants. The principal sources of nicotine exposure are through the use of tobacco, nicotine containing gum and nicotine replacement therapies. Nicotine is an amine composed of pyridine and pyrrolidine rings. It has been shown that nicotine crosses biological membranes and the blood brain barrier easily. The absorbed nicotine is extensively metabolized in the liver to form a wide variety of metabolites including and cotinine N-oxide. Nicotine has been shown to affect a wide variety of biological functions ranging from gene expression, regulation of hormone secretion and enzyme activities. (PMID: 16359169 , 15109883 ).
Structure
Thumb
Synonyms
ValueSource
(5S)-1-Methyl-5-(1-oxido-3-pyridinyl)-2-pyrrolidinoneMetaCyc
(S)-1-Methyl-5-(1-oxido-3-pyridinyl)-2-pyrrolidinoneHMDB
(S)-1-Methyl-5-(3-pyridinyl)-2-pyrrolidinone N-oxideHMDB
Cotinine-N-oxideHMDB
Chemical FormulaC10H12N2O2
Average Molecular Weight192.2145
Monoisotopic Molecular Weight192.089877638
IUPAC Name3-[(2S)-1-methyl-5-oxopyrrolidin-2-yl]pyridin-1-ium-1-olate
Traditional Name3-[(2S)-1-methyl-5-oxopyrrolidin-2-yl]pyridin-1-ium-1-olate
CAS Registry Number36508-80-2
SMILES
CN1[C@@H](CCC1=O)C1=C[N+]([O-])=CC=C1
InChI Identifier
InChI=1S/C10H12N2O2/c1-11-9(4-5-10(11)13)8-3-2-6-12(14)7-8/h2-3,6-7,9H,4-5H2,1H3/t9-/m0/s1
InChI KeyInChIKey=CIPULDKLIIVIER-VIFPVBQESA-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
  • Pyridinium
  • Pyridine
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Drug metabolite
  • Endogenous
Biofunction
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility11.0 mg/mLALOGPS
logP-0.66ALOGPS
logP-1ChemAxon
logS-1.2ALOGPS
pKa (Strongest Basic)0.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area45.77 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity52.97 m3·mol-1ChemAxon
Polarizability19.5 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Nicotine Metabolism PathwaySMP00628Not Available
Nicotine PathwaySMP00431Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000017 +/- 0.000006 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.24 +/- 0.19 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00529
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022606
KNApSAcK IDNot Available
Chemspider ID7991264
KEGG Compound IDNot Available
BioCyc IDCPD-3185
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB01411
Metagene LinkHMDB01411
METLIN ID6227
PubChem Compound9815514
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceRiah, Omar; Dousset, Jean Claude; Courriere, Philippe; Baziard-Mouysset, Genevieve; Ecalle, Rene. Synthesis of cotinine and cotinine N-oxide. Evaluation of their interaction with nicotine in the insecticidal activity. Natural Product Letters (1997), 11(1), 37-45.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Xu X, Iba MM, Weisel CP: Simultaneous and sensitive measurement of anabasine, nicotine, and nicotine metabolites in human urine by liquid chromatography-tandem mass spectrometry. Clin Chem. 2004 Dec;50(12):2323-30. Epub 2004 Oct 7. [15472033 ]
  2. Zuccaro P, Altieri I, Rosa M, Passa AR, Pichini S, Ricciarello G, Pacifici R: Determination of nicotine and four metabolites in the serum of smokers by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 1993 Nov 24;621(2):257-61. [8294547 ]
  3. Jacob P 3rd, Shulgin AT, Yu L, Benowitz NL: Determination of the nicotine metabolite trans-3'-hydroxycotinine in urine of smokers using gas chromatography with nitrogen-selective detection or selected ion monitoring. J Chromatogr. 1992 Dec 2;583(2):145-54. [1478978 ]
  4. Brown KM, von Weymarn LB, Murphy SE: Identification of N-(hydroxymethyl) norcotinine as a major product of cytochrome P450 2A6, but not cytochrome P450 2A13-catalyzed cotinine metabolism. Chem Res Toxicol. 2005 Dec;18(12):1792-8. [16359169 ]
  5. Yildiz D: Nicotine, its metabolism and an overview of its biological effects. Toxicon. 2004 May;43(6):619-32. [15109883 ]