LC-MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study

Biomed Chromatogr. 2014 Sep;28(9):1173-82. doi: 10.1002/bmc.3139. Epub 2014 Apr 7.

Abstract

Three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3-methyl-1-p-tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB-Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid-methanol, isocratic 0.1% formic acid-methanol (90:10) and 0.02% formic acid-methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H](+) 175.1 → 133.0 and [M + H](+) 189.2 → 147.0 for edaravone and its IS, m/z [M - H](-) 124.1 → 80.0 and [M - H](-) 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co-administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration-time curve, mean residence time, half-life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.

Keywords: LC-MS/MS; edaravone; intravenous administration; pharmacokinetic; taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antipyrine / administration & dosage
  • Antipyrine / analogs & derivatives*
  • Antipyrine / blood
  • Antipyrine / chemistry
  • Antipyrine / pharmacokinetics
  • Chromatography, Liquid / methods*
  • Drug Interactions
  • Edaravone
  • Limit of Detection
  • Linear Models
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*
  • Taurine / administration & dosage
  • Taurine / blood*
  • Taurine / chemistry
  • Taurine / pharmacokinetics

Substances

  • Taurine
  • Edaravone
  • Antipyrine