Determination of a new thymidine phosphorylase inhibitor, TPI, in dog and rat plasma by reversed-phase ion-pair high-performance liquid chromatography |
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| Authors: | Takashi Kawauchi Hiroshi Matsumoto Shingo Yano |
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| Institution: | 1. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance - Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany;2. Institute for Occupational and Maritime Medicine (ZfAM), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany;3. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA;4. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA;5. German Environment Agency (UBA), Berlin, Germany;6. Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark;7. Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, Oslo, Norway;8. Department of Health Sciences, Karlstad University, Karlstad, Sweden;9. Queensland Alliance for Environmental Health Sciences, The University of Queensland, Brisbane, Australia;10. Silent Spring Institute, Newton, MA, USA;11. Department of Epidemiology, Brown University School of Public Health, Providence, USA |
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| Abstract: | A high-performance liquid chromatographic method for the determination of a new thymidine phosphorylase inhibitor, TPI, in dog and rat plasma is described. TPI was isolated from biological samples by solid-phase extraction on Bond Elut PRS columns. Chromatographic separation was achieved on a C18 column using a mobile phase consisting of acetonitrile–10 mM acetate buffer (pH 4.3) including hexanesulfonate, with UV detection at 276 nm. This method has been validated across the range of 50–50 000 ng/ml using a 0.1-ml plasma volume. The mean recoveries from spiked plasma were 93% for dog and 94% for rat, respectively. The accuracy, precision and specificity of the method were demonstrated to be acceptable, and it was applied to the toxicokinetic study of TPI in rats. |
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| Keywords: | Thymidine phosphorylase inhibitor 5-Chloro-6-(2-iminopyrrolidin-1-yl)methyl-2 4(1H 3H)-pyrimidinedione hydrochloride |
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