Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Use of Human Microsomes and Deuterated Substrates: An Alternative Approach for the Identification of Novel Metabolites of Ketamine by Mass Spectrometry

Sophie C. Turfus, Mark C. Parkin, David A. Cowan, John M. Halket, Norman W. Smith, Robin A. Braithwaite, Simon P. Elliot, Glyn B. Steventon and Andrew T. Kicman
Drug Metabolism and Disposition August 2009, 37 (8) 1769-1778; DOI: https://doi.org/10.1124/dmd.108.026328
Sophie C. Turfus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark C. Parkin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Cowan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John M. Halket
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Norman W. Smith
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robin A. Braithwaite
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon P. Elliot
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Glyn B. Steventon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew T. Kicman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

In vitro biosynthesis using pooled human liver microsomes was applied to help identify in vivo metabolites of ketamine by liquid chromatography (LC)-tandem mass spectrometry. Microsomal synthesis produced dehydronorketamine, seven structural isomers of hydroxynorketamine, and at least five structural isomers of hydroxyketamine. To aid identification, stable isotopes of the metabolites were also produced from tetra-deuterated isotopes of ketamine or norketamine as substrates. Five metabolites (three hydroxynorketamine and two hydroxyketamine isomers) gave chromatographically resolved components with product ion spectra indicating the presence of a phenolic group, with phenolic metabolites being further substantiated by selective liquid-liquid extraction after adjustments to the pH. Two glucuronide conjugates of hydroxynorketamine were also identified. Analysis by LC-coupled ion cyclotron resonance mass spectrometry gave unique masses in accordance with the predicted elemental composition. The metabolites, including the phenols, were subsequently confirmed to be present in urine of subjects after oral ketamine administration, as facilitated by the addition of deuterated metabolites generated from the in vitro biosynthesis. To our knowledge, phenolic metabolites of ketamine, including an intact glucuronide conjugate, are here reported for the first time. The use of biologically synthesized deuterated material as an internal chromatographic and mass spectrometric marker is a viable approach to aid in the identification of metabolites. Metabolites that have particular diagnostic value can be selected as candidates for chemical synthesis of standards.

Footnotes

  • This work was supported by the Engineering and Physical Sciences Research Council [Grant Think Crime EP/C533437/1].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.026328.

  • ABBREVIATIONS: MS/MS, tandem mass spectrometry; HPLC, high-performance liquid chromatography; SPE, solid-phase extraction; SRM, selected reaction monitoring; MS, mass spectrometry; LC, liquid chromatography; FT, Fourier transform; ICR, ion cyclotron resonance; HNK, hydroxynorketamine.

    • Accepted May 15, 2009.
    • Received December 19, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 37 (8)
Drug Metabolism and Disposition
Vol. 37, Issue 8
1 Aug 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Use of Human Microsomes and Deuterated Substrates: An Alternative Approach for the Identification of Novel Metabolites of Ketamine by Mass Spectrometry
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Use of Human Microsomes and Deuterated Substrates: An Alternative Approach for the Identification of Novel Metabolites of Ketamine by Mass Spectrometry

Sophie C. Turfus, Mark C. Parkin, David A. Cowan, John M. Halket, Norman W. Smith, Robin A. Braithwaite, Simon P. Elliot, Glyn B. Steventon and Andrew T. Kicman
Drug Metabolism and Disposition August 1, 2009, 37 (8) 1769-1778; DOI: https://doi.org/10.1124/dmd.108.026328

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Use of Human Microsomes and Deuterated Substrates: An Alternative Approach for the Identification of Novel Metabolites of Ketamine by Mass Spectrometry

Sophie C. Turfus, Mark C. Parkin, David A. Cowan, John M. Halket, Norman W. Smith, Robin A. Braithwaite, Simon P. Elliot, Glyn B. Steventon and Andrew T. Kicman
Drug Metabolism and Disposition August 1, 2009, 37 (8) 1769-1778; DOI: https://doi.org/10.1124/dmd.108.026328
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Determination of Acyl-, O-, and N-Glucuronide
  • TMDD Affects PK of IL-10 Fc-fusion Proteins
  • Uptake as the RDS in Pevonedistat Hepatic Clearance
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics