Determination of 3-methoxysalicylamine levels in mouse plasma and tissue by liquid chromatography-tandem mass spectrometry: application to in vivo pharmacokinetics studies

J Chromatogr B Analyt Technol Biomed Life Sci. 2011 May 1;879(15-16):1098-104. doi: 10.1016/j.jchromb.2011.03.026. Epub 2011 Mar 21.

Abstract

We report the development of a sensitive liquid chromatography-tandem mass spectrometric assay to quantitate 3-methoxysalicylamine (3-MoSA) in biological samples. Derivatization with 1,1'-thiocarbonyldiimidazole followed by C(18) reverse-phase chromatography allowed the detection of both analyte and internal standard (hexylsalicylamine) using electrospray ionization and selected reaction monitoring (SRM) in positive ion mode. We monitored the transitions from m/z 196.7 to 65.1 and from m/z 250.1 to 77.1 for 3-MoSA and HxSA, respectively. The method is validated with respect to linearity (r(2)=0.995), precision (<17% RSD), recovery (100% for 3-MoSA and HxSA), and stability (77% after storage up to 7 month at -80°C). The LOD and LOQ were 16.12 and 48.87 μg/l, respectively and the LLOQ of 1 pg/ml. In addition, we used this assay to analyze the pharmacokinetics of 3-MoSA in mouse plasma and tissues following both intraperitoneal and oral administration, providing new information regarding the distribution of this compound in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aminosalicylic Acids / administration & dosage
  • Aminosalicylic Acids / analysis*
  • Aminosalicylic Acids / blood*
  • Aminosalicylic Acids / pharmacokinetics
  • Animals
  • Benzylamines / administration & dosage
  • Benzylamines / analysis*
  • Benzylamines / blood
  • Benzylamines / pharmacokinetics*
  • Brain / metabolism*
  • Brain Chemistry
  • Chromatography, Liquid / methods*
  • Injections, Intraperitoneal
  • Linear Models
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Tandem Mass Spectrometry / methods*
  • Tissue Distribution

Substances

  • 3-methoxysalicylamine
  • Aminosalicylic Acids
  • Benzylamines