期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 70, 期 -, 页码 499-504出版社
ELSEVIER
DOI: 10.1016/j.jpba.2012.07.016
关键词
UPLC-MS/MS; Pharmacokinetics; FMISO; Dose-response relationships; PET
资金
- National 973 Program [2011CB504105]
- National 863 Program [SS2012AA020831]
- Open Foundation of the Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing Capital Medical University
Screening the pharmacokinetics of candidates using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) may be efficacious and safe for the research and development of new PET imaging agents. However, the PET imaging agent is administered as trace dose and the sensitivity of LC-MS/MS is often insufficient. If the dose was increased to be quantifiable, it should be necessary to prove whether the pharmacokinetics between trace and macro-doses is consistent or not. In this paper, fluoromisonidazole (FMISO), a tumor PET imaging agent, was chosen to evaluate the dose-response pharmacokinetics by administering various single intravenous doses (0.1, 0.4, 1.6 and 6.4 mg/kg) in male Sprague-Dawley rats. The plasma concentration of FMISO was determined by an ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method, and the blood radioactivity of [F-18]FMISO was detected by a gamma counter. By calculating and comparing the pharmacokinetic parameters. the total area under the plasma concentration-time curve from time zero to infinity (AUC(0-infinity)) and peak plasma concentration (C-max) values increased with the selected FMISO doses, and showing linear dose-dependent. On the other hand, some parameters related to time, such as the elimination half-lives (t(1/2)) and elimination rate constant (K-e) were dose-independent, and there is no significant deference between trace dose and various macro-doses. The data should be useful to evaluate the novel 2-nitroimidazole derivatives as potential PET tumor imaging agents. (C) 2012 Elsevier B.V. All rights reserved.
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