Liquid chromatography-tandem mass spectrometric assay for the quantitation of the novel radiation protective agent and radiation mitigator JP4-039 in murine plasma
| Autor: | Jianxia Guo, Adam T. Hoye, Jan H. Beumer, Peter Wipf, Susan M. Christner, Julie L. Eiseman, Joel S. Greenberger, Melanie Ringeval, Robert A. Parise, Michael W. Epperly |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Electrospray Spectrometry Mass Electrospray Ionization Clinical Biochemistry Pharmaceutical Science Radiation-Protective Agents Tandem mass spectrometry Article Analytical Chemistry Ionizing radiation 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Drug Stability Tandem Mass Spectrometry Ionization Drug Discovery Protein precipitation Animals Spectroscopy Chromatography Reverse-Phase Chromatography Chemistry Reproducibility of Results Reversed-phase chromatography Plasma Reference Standards Cold Temperature Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis Calibration Administration Intravenous Nitrogen Oxides Drug Monitoring |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 150 |
| ISSN: | 1873-264X |
| Popis: | JP4-039 radio-protects prior to, and radio-mitigates after ionizing radiation by neutralizing reactive oxygen species. We developed and validated an LC-MS/MS assay for the quantitation of JP4-039 in murine plasma. Methanol protein precipitation of 50 μL plasma was followed by isocratic reverse phase chromatography for a 6 min run time, and electrospray positive mode ionization mass spectrometric detection. The plasma assay was linear from 1–1000 ng/mL with appropriate accuracy (97.1–107.6%) and precision (3.7–12.5%CV), and fulfilled FDA guidance criteria. Recovery was 77.2–136.1% with moderate ionization enhancement (10.9–39.5%). Plasma freeze-thaw stability (98.8–104.2%), stability for 13.5 months at −80 °C (93.1–105.6%), and stability for 4 h at room temperature (94.2–97.6%) were all acceptable. Limited cross-validation to tissue homogenates suggested that these could also be analyzed for JP4-039 accurately. This assay has been directly applied to determine the pharmacokinetics of JP4-039 in C57BL/6 male mice after IV administration of 20 mg/kg JP4-039 and will be extended to other studies of this agent. |
| Databáze: | OpenAIRE |
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