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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2021-09-14 15:45:00 UTC
HMDB IDHMDB0001390
Secondary Accession Numbers
  • HMDB01390
Metabolite Identification
Common NameHydroxycotinine
DescriptionHydroxycotinine 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 excreted as a glucuronide conjugate (3HC-Gluc). Hydroxycotinine is a strong basic compound (based on its pKa). hydroxycotinine can be biosynthesized from cotinine through its interaction with the enzyme cytochrome P450 2A6. In humans, hydroxycotinine is involved in nicotine metabolism pathway. Hydroxycotinine (3HC) is the main nicotine metabolite detected in smokers urine. Quantitatively, the most important metabolite of nicotine in most mammalian species is cotinine. 3HC and 3HC-Gluc account for 40-60% of the nicotine dose in urine.
Structure
Data?1582752197
Synonyms
ValueSource
(3R-trans)-3-Hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinoneHMDB
3-Hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinoneHMDB
3-HydroxycotinineHMDB
trans-3'-HydroxycotinineHMDB
trans-3-HydroxycotinineHMDB
1-Methyl-3-hydroxy-5-(3-pyridyl)-2-pyrrolidinoneHMDB
3'-HydroxycotinineHMDB
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 Namehydroxycotinine
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
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
  • Carboxamide group
  • Lactam
  • Secondary alcohol
  • Carboxylic acid derivative
  • Azacycle
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Carbonyl group
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP-1.45LI,NY & GORROD,JW (1992)
Experimental Chromatographic PropertiesNot Available
Predicted Molecular 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 Area53.43 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity50.73 m³·mol⁻¹ChemAxon
Polarizability19.48 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+142.22731661259
DarkChem[M-H]-140.7731661259
AllCCS[M+H]+143.0232859911
AllCCS[M-H]-143.55432859911
DeepCCS[M+H]+145.96630932474
DeepCCS[M-H]-143.5730932474
DeepCCS[M-2H]-177.05130932474
DeepCCS[M+Na]+151.930932474
AllCCS[M+H]+143.032859911
AllCCS[M+H-H2O]+138.632859911
AllCCS[M+NH4]+147.132859911
AllCCS[M+Na]+148.332859911
AllCCS[M-H]-143.632859911
AllCCS[M+Na-2H]-143.932859911
AllCCS[M+HCOO]-144.432859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
HydroxycotinineCN1[C@@H](CC(O)C1=O)C1=CN=CC=C12713.8Standard polar33892256
HydroxycotinineCN1[C@@H](CC(O)C1=O)C1=CN=CC=C11837.3Standard non polar33892256
HydroxycotinineCN1[C@@H](CC(O)C1=O)C1=CN=CC=C11814.1Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Hydroxycotinine,1TMS,isomer #1CN1C(=O)C(O[Si](C)(C)C)C[C@H]1C1=CC=CN=C11831.1Semi standard non polar33892256
Hydroxycotinine,1TBDMS,isomer #1CN1C(=O)C(O[Si](C)(C)C(C)(C)C)C[C@H]1C1=CC=CN=C12039.5Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Hydroxycotinine GC-MS (Non-derivatized) - 70eV, Positivesplash10-0kgy-3900000000-f4341e07a5c7a80b75362017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Hydroxycotinine GC-MS (1 TMS) - 70eV, Positivesplash10-0kmv-7920000000-c5ea44b12e63e343fb9a2017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Hydroxycotinine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Hydroxycotinine 0V, Positive-QTOFsplash10-0006-0900000000-eb516ddd256ff613e87d2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Hydroxycotinine 30V, Positive-QTOFsplash10-053r-9300000000-f280be49213ae3a130792021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Hydroxycotinine 0V, Positive-QTOFsplash10-0006-0900000000-7bda1053fba136e847962021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Hydroxycotinine 10V, Positive-QTOFsplash10-0006-0900000000-1c333f7a47d4c50ba1472021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Hydroxycotinine 30V, Positive-QTOFsplash10-001i-9200000000-764ed8e56080570ebb2b2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Hydroxycotinine 10V, Positive-QTOFsplash10-000l-2900000000-bb4782c424b825499da92021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 10V, Positive-QTOFsplash10-0006-0900000000-e71a8aefcc63f8da573f2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 20V, Positive-QTOFsplash10-002f-0900000000-9c8836e76f228880b9ef2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 40V, Positive-QTOFsplash10-0006-9700000000-ac3865df5f81a068cc892017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 10V, Negative-QTOFsplash10-0006-0900000000-422cb094c7d4df4e90322017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 20V, Negative-QTOFsplash10-0006-1900000000-455cd9052e09eb5156d22017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 40V, Negative-QTOFsplash10-004i-9800000000-dbdfb504e7cdb984dc832017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 10V, Positive-QTOFsplash10-0006-0900000000-0827985d284ee48475872021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 20V, Positive-QTOFsplash10-002f-0900000000-b7907c9e2b16530e96362021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 40V, Positive-QTOFsplash10-0a5c-5900000000-aeeff361755465a46a0a2021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 10V, Negative-QTOFsplash10-0006-0900000000-0bb6b33191167fa82f572021-09-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 20V, Negative-QTOFsplash10-0fi3-3900000000-94e7e72f592f380dfd372021-09-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Hydroxycotinine 40V, Negative-QTOFsplash10-0ufr-8900000000-343920275b5ee98bf6ac2021-09-25Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted 1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-25Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Saliva
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.25 +/- 0.045 uMAdult (>18 years old)BothNormal 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 Quantified0.35 +/- 0.15 uMAdult (>18 years old)BothSmoking details
BloodDetected and Quantified1.5 (0.52-2.6) uMAdult (>18 years old)BothActive tobacco user details
UrineDetected and Quantified4.5 (1.0-8.5) umol/mmol creatinineAdult (>18 years old)BothActive tobacco user details
Associated Disorders and Diseases
Disease References
Smoking
  1. 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 ]
  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 ]
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022597
KNApSAcK IDNot Available
Chemspider ID8395266
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID6210
PubChem Compound10219774
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000320
Good Scents 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. J. Med. Chem. (1990), 33 (7), pp 1888–1891
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. 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

General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid.
Gene Name:
UGT2B4
Uniprot ID:
P06133
Molecular weight:
60512.035
References
  1. Yamanaka H, Nakajima M, Katoh M, Kanoh A, Tamura O, Ishibashi H, Yokoi T: Trans-3'-hydroxycotinine O- and N-glucuronidations in human liver microsomes. Drug Metab Dispos. 2005 Jan;33(1):23-30. Epub 2004 Oct 6. [PubMed:15470160 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular weight:
60024.535
References
  1. Yamanaka H, Nakajima M, Katoh M, Kanoh A, Tamura O, Ishibashi H, Yokoi T: Trans-3'-hydroxycotinine O- and N-glucuronidations in human liver microsomes. Drug Metab Dispos. 2005 Jan;33(1):23-30. Epub 2004 Oct 6. [PubMed:15470160 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular weight:
60720.15
References
  1. Yamanaka H, Nakajima M, Katoh M, Kanoh A, Tamura O, Ishibashi H, Yokoi T: Trans-3'-hydroxycotinine O- and N-glucuronidations in human liver microsomes. Drug Metab Dispos. 2005 Jan;33(1):23-30. Epub 2004 Oct 6. [PubMed:15470160 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
References
  1. Yamanaka H, Nakajima M, Katoh M, Kanoh A, Tamura O, Ishibashi H, Yokoi T: Trans-3'-hydroxycotinine O- and N-glucuronidations in human liver microsomes. Drug Metab Dispos. 2005 Jan;33(1):23-30. Epub 2004 Oct 6. [PubMed:15470160 ]