Analysis of a novel antiinflammatory agent, 1-(7-tert.-butyl-2,3-dihydro-3,3-dimethylbenzo[b]furan-5-yl)-4- cyclopylbutan-1-one (PGV-20229), in plasma matrices by stable-isotope-dilution gas chromatography-mass spectrometry

J Chromatogr B Biomed Sci Appl. 1997 Oct 24;700(1-2):111-8. doi: 10.1016/s0378-4347(97)00320-4.

Abstract

A sensitive and selective GC-MS method was developed for the determination of low levels of a novel antiinflammatory agent, 1-(7-tert.-butyl-2,3-dihydro-3,3-dimethylbenzo[b]furan-5-yl)-4- cyclopropylbutan-1-one (I), in small volumes of animal plasma. The method involved the addition of 13C6-labeled-I to plasma samples, followed by a simple liquid-liquid extraction with hexane to isolate the analytes from matrix components. The levels of I in the sample extracts were determined by isotope-dilution GC-MS analysis using selected-ion monitoring. The method was linear over three orders of magnitude, with a limit of quantitation of 1.8 ng/ml I, using plasma sample volumes of 0.1 ml. The method was utilized to determine the pharmacokinetic parameters of I in rats and dogs, following intravenous administration.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / blood*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Benzofurans / blood*
  • Benzofurans / pharmacokinetics
  • Carbon Isotopes
  • Dogs
  • Drug Stability
  • Gas Chromatography-Mass Spectrometry
  • Indicator Dilution Techniques
  • Male
  • Phenols / blood*
  • Phenols / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzofurans
  • Carbon Isotopes
  • PGV 20229
  • Phenols