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

Hari Kosanam, Fei Ma, Hui He, Suma Ramagiri, Veeresa Gududuru, Gabor Tigyi, Koen Van Rompay, Duane Miller, Charles Yates

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2379-2383
Number of pages5
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume878
Issue number26
DOIs
StatePublished - Sep 1 2010

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Pharmacokinetics
Haplorhini
Assays
Plasmas
Liquid chromatography
Dosimetry
Lysophospholipids
Electrospray ionization
Butanols
Liquid-Liquid Extraction
Whole-Body Irradiation
Liquids
Mass spectrometers
Reverse-Phase Chromatography
Tandem Mass Spectrometry
thiophosphoric acid
Liquid Chromatography
Mass spectrometry
Half-Life
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Development of an LC-MS/MS assay to determine plasma pharmacokinetics of the radioprotectant octadecyl thiophosphate (OTP) in monkeys. / Kosanam, Hari; Ma, Fei; He, Hui; Ramagiri, Suma; Gududuru, Veeresa; Tigyi, Gabor; Van Rompay, Koen; Miller, Duane; Yates, Charles.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 878, No. 26, 01.09.2010, p. 2379-2383.

Research output: Contribution to journalArticle

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