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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.

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

Author information

1
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Advanced Cancer Detection Center, Samuel Lunenfeld Research Institute, Toronto, ON, Canada.

Abstract

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.

PMID:
20719582
PMCID:
PMC2965032
DOI:
10.1016/j.jchromb.2010.07.004
[Indexed for MEDLINE]
Free PMC Article

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