uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A mass spectromeric study on meloxicam metabolism in horses and the fungus Cunninghamella elegans, and the relevance of this microbial system as a model of drug metabolism in the horse
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
2009 (English)In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 44, no 7, 1026-1037 p.Article in journal (Refereed) Published
Abstract [en]

This paper describes a study where the metabolism of the non-steroidal   anti-inflammatory drug meloxicam was investigated in six horses and in  the filamentous fungus Cunninghamella elegans. The metabolites identified were compared between the species, and then the fungus was  used to produce larger amounts of the metabolites for future use as   reference material. C. elegans proved to be a good model of phase I   meloxicam metabolism in horses since all four metabolites found were   the same in both species. Apart from the two main metabolites,   5'-hydroxymethylmeloxicam and 5'-carboxymeloxicam, a second isomer of   hydroxymeloxicam and dihydroxylated meloxicam were detected for the   first time in horse urine and the microbial incubations. Phase II   metabolites were not discovered in the C. elegans samples but   hydroxymeloxicam glucuronide was detected intact in horse urine for the   first time in this study. Urine from six horses was further analyzed in   a semi-quantitative sense and 5'-hydroxymethylmeloxicam gave peaks with   much higher intensity compared to the parent drug and the other   metabolites, and was detected for at least 14 days after the last given   dose in some of the horses. From the results presented in this article,   we suggest that analytical methods developed for the detection of   meloxicam in horse urine after prohibited use should focus on the   5'-hydroxymethyl metabolite and that C. elegans can be used to produce  large amounts of this metabolite for potential future use as a reference compound.

Place, publisher, year, edition, pages
2009. Vol. 44, no 7, 1026-1037 p.
Keyword [en]
Meloxicam, metabolism, mass spectrometry, horse, Cunninghamella elegans
National Category
Pharmaceutical Sciences
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-98287DOI: 10.1002/jms.1575ISI: 000268505500003OAI: oai:DiVA.org:uu-98287DiVA: diva2:174192
Available from: 2009-02-19 Created: 2009-02-18 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Detection and Structure Elucidation of Drug Metabolites in Biological Samples using HPLC-MS/MS Techniques
Open this publication in new window or tab >>Detection and Structure Elucidation of Drug Metabolites in Biological Samples using HPLC-MS/MS Techniques
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the structure elucidation of drug metabolites in biological samples by the use of high performance liquid chromatography (HPLC) atmospheric pressure ionization (API) tandem mass spectrometry (MS/MS). Due to their different advantages, various mass analyzers have been used in the different experiments.

The metabolism of clemastine, flutamide, and meloxicam were studied in vitro and/or in vivo in different species such as humans, dogs, and horses. Accurate mass measurements with the quadrupole-time of flight mass spectrometer and MSn data supplied by the ion trap instrument were useful in the structural investigation of the product ions of the drugs and their metabolites. Different scan modes of the triple quadrupole mass spectrometer resulted in great flexibility, selectivity, and sensitivity in the qualitative and semi-quantitative studies. Additionally, hydrogen/deuterium exchange and experiments with atmospheric pressure chemical ionization were conducted, and the fungus Cunninghamella elegans was utilized to produce amounts of drug metabolites sufficient for structural investigation.

Six isomers of oxidized clemastine were detected and characterized in C. elegans incubations and their retention times and mass spectral data were compared to the metabolites detected in urine samples. Two of the metabolites were concluded to be diastereomeric N-oxides.

In urine from horses treated with meloxicam, the peak of 5'-hydroxymethylmeloxicam resulted in much higher intensity than the parent drug or the other metabolites, and it was detectable for at least 14 days after the last dose in some of the horses. That is useful information in the development of analytical methods for the detection of prohibited use of meloxicam.

A mercapturic acid conjugate of hydroxyflutamide was detected in urine from cancer patients, which indicated that a reactive metabolite was formed. This metabolite could be responsible for the adverse events reported for flutamide.

The results from the four papers included in the thesis clearly demonstrate the usefulness and the flexibility of the HPLC-API-MS/MS technique.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 73 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 90
National Category
Medicinal Chemistry
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
urn:nbn:se:uu:diva-98348 (URN)978-91-554-7437-9 (ISBN)
Public defence
2009-04-03, B22, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-03-13 Created: 2009-02-19 Last updated: 2009-03-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
Analytical Pharmaceutical Chemistry
In the same journal
Journal of Mass Spectrometry
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 573 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf