Detection of nimesulide metabolites in rat plasma and hepatic subcellular fractions by HPLC-UV/DAD and LC-MS/MS studies

Ş Güniz Küçükgüzel, Ilkay Küçükgüzel, Başak Oral, Sena Sezen, Sevim Rollas

Research output: Contribution to journalArticle

Abstract

Nimesulide (4-nitro-2-phenoxymethanesulfonanilide) is an atypical NSAID lacking a carboxylic acid moiety. It has a good gastric tolerability due to selective inhibition of COX-2. The study objectives in the present work were to characterize the metabolism of nimesulide in rat plasma at certain time intervals. In vitro studies were also carried out to examine if nitroreduction takes place in vitro using rat hepatic subcellular fractions (microsomal and S9 fraction) besides aromatic hydroxylation. This communication describes detection and characterization of nimesulide metabolites isolated from plasma and hepatic subcellular post-incubates by the use of HPLC-UV/diode array and LC-MS/MS. Hydroxynimesulide was the major metabolite both in vivo and in vitro whereas nitroreduction was observed only in vitro with subcellular fractions under anaerobic conditions.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume30
Issue number1-2
Publication statusPublished - Jan 2005
Externally publishedYes

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Keywords

  • LC-MS/MS
  • Nimesulide
  • Nitroarenes
  • Nitroreduction
  • S9 fraction

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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