Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:10:27 UTC
HMDB IDHMDB01390
Secondary Accession NumbersNone
Metabolite Identification
Common NameHydroxycotinine
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. 3-Hydroxycotinine (3HC) is the main nicotine metabolite detected in smokers urine. It is also excreted as a glucuronide conjugate (3HC-Gluc). 3HC and 3HC-Gluc account for 40-60% of the nicotine dose in urine.
Structure
Thumb
Synonyms
  1. (3R-trans)-3-hydroxy-1-methyl-5-(3-pyridinyl)-2-Pyrrolidinone
  2. 3-Hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone
  3. 3-Hydroxycotinine
  4. trans-3'-Hydroxycotinine
  5. trans-3-Hydroxycotinine
Chemical FormulaC10H12N2O2
Average Molecular Weight192.2145
Monoisotopic Molecular Weight192.089877638
IUPAC Name(5S)-3-hydroxy-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
Traditional IUPAC Name(5S)-3-hydroxy-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
CAS Registry Number34834-67-8
SMILES
CN1[C@@H](CC(O)C1=O)C1=CN=CC=C1
InChI Identifier
InChI=1S/C10H12N2O2/c1-12-8(5-9(13)10(12)14)7-3-2-4-11-6-7/h2-4,6,8-9,13H,5H2,1H3/t8-,9?/m0/s1
InChI KeyXOKCJXZZNAUIQN-IENPIDJESA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAlkaloids and Derivatives
ClassN/A
Sub ClassN/A
Other Descriptors
  • Pyrrolidinylpyridines
Substituents
  • Carboxamide Group
  • Lactam
  • Pyridine
  • Pyrrolidine
  • Pyrrolidone
  • Secondary Alcohol
  • Tertiary Carboxylic Acid Amide
Direct ParentAlkaloids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Drug metabolite
  • Endogenous
Biofunction
  • Waste products
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP-1.45LI,NY & GORROD,JW (1992)
Predicted Properties
PropertyValueSource
water solubility47.7 g/LALOGPS
logP-0.32ALOGPS
logP-0.73ChemAxon
logS-0.61ALOGPS
pKa (strongest acidic)13.11ChemAxon
pKa (strongest basic)4.79ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area53.43ChemAxon
rotatable bond count1ChemAxon
refractivity50.73ChemAxon
polarizability19.48ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Kidney
  • Liver
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified0.35 +/- 0.15 uMAdult (>18 years old)BothNormal
BloodDetected and Quantified0.25 +/- 0.045 uMAdult (>18 years old)BothNormal
SalivaDetected and Quantified<1.00 uMAdult (>18 years old)BothNormal
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified1.5 (0.52-2.6) uMAdult (>18 years old)BothActive tobacco user
UrineDetected and Quantified4.5 (1.0-8.5) umol/mmol creatinineAdult (>18 years old)BothActive tobacco user
Associated Disorders and Diseases
Disease References
Smoking
  • 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. Pubmed: 8294547
  • 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
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00527
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022597
KNApSAcK IDNot Available
Chemspider ID8395266
KEGG Compound IDNot Available
BioCyc IDCPD-2750
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB01390
Metagene LinkHMDB01390
METLIN ID6210
PubChem Compound10219774
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceJacob, Peyton, III; Shulgin, Alexander T.; Benowitz, Neal L. Synthesis of (3'R,5'S)-trans-3'-hydroxycotinine, a major metabolite of nicotine. Metabolic formation of 3'-hydroxycotinine in humans is highly stereoselective. Journal of Medicinal Chemistry (19
Material Safety Data Sheet (MSDS)Not Available
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. 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
  3. 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. Pubmed: 15472033
  4. Kim I, Huestis MA: A validated method for the determination of nicotine, cotinine, trans-3'-hydroxycotinine, and norcotinine in human plasma using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. J Mass Spectrom. 2006 Jun;41(6):815-21. Pubmed: 16705667
  5. Pacifici R, Pichini S, Altieri I, Rosa M, Bacosi A, Caronna A, Zuccaro P: Determination of nicotine and two major metabolites in serum by solid-phase extraction and high-performance liquid chromatography, and high-performance liquid chromatography-particle beam mass spectrometry. J Chromatogr. 1993 Feb 26;612(2):209-13. Pubmed: 8468378
  6. Tuomi T, Johnsson T, Reijula K: Analysis of nicotine, 3-hydroxycotinine, cotinine, and caffeine in urine of passive smokers by HPLC-tandem mass spectrometry. Clin Chem. 1999 Dec;45(12):2164-72. Pubmed: 10585349
  7. Lerman C, Tyndale R, Patterson F, Wileyto EP, Shields PG, Pinto A, Benowitz N: Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther. 2006 Jun;79(6):600-8. Epub 2006 May 11. Pubmed: 16765148

Enzymes

Gene Name:
UGT2B4
Uniprot ID:
P06133
Gene Name:
UGT1A4
Uniprot ID:
P22310
Gene Name:
UGT2B7
Uniprot ID:
P16662
Gene Name:
UGT1A9
Uniprot ID:
O60656