Development of an LC-MS/MS assay to determine plasma pharmacokinetics of the radioprotectant octadecenyl thiophosphate (OTP) in monkeys

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 15;878(26):2379-83. doi: 10.1016/j.jchromb.2010.07.004. Epub 2010 Jul 18.


Octadecenyl thiophosphate (OTP), a synthetic analogue of the lysophospholipid growth factor lysophosphatidic acid (LPA), significantly reduces mortality following a lethal dose of LD(80/30) radiation exposure in a mouse model of whole-body irradiation. To facilitate dose scaling between species, we developed a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) for the preclinical pharmacokinetic characterization of OTP in monkeys. Sample extraction was carried out using a butanol based liquid-liquid extraction method. A partially deuterated OTP analogue was used as internal standard (IS). OTP and IS were separated by reversed-phase liquid chromatography on a C-8 column using 10mM ammonium acetate and acetonitrile. A triple quadrupole mass spectrometer operating in the negative electrospray ionization mode with multiple reaction monitoring was used to detect OTP and IS transitions of m/z 363.1-->95.0 and 403.1-->95.0. The method was applied to determine pharmacokinetic parameters in monkeys receiving a single oral OTP dose (3mg/kg). OTP is readily absorbed with a relatively long half-life which supports further preclinical testing of OTP as a radioprotectant in monkeys.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Butanols / chemistry
  • Chemical Fractionation
  • Chromatography, Liquid / methods*
  • Drug Stability
  • Female
  • Linear Models
  • Macaca mulatta
  • Organophosphorus Compounds / blood
  • Organophosphorus Compounds / pharmacokinetics*
  • Radiation-Protective Agents / analysis
  • Radiation-Protective Agents / pharmacokinetics*
  • Reference Standards
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*


  • Butanols
  • Organophosphorus Compounds
  • Radiation-Protective Agents
  • octadecenyl thiophosphate