Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7632785 | Journal of Pharmaceutical and Biomedical Analysis | 2012 | 6 Pages |
Abstract
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 6.4Â 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 [18F]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 (AUC0-â) and peak plasma concentration (Cmax) 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 (t1/2) and elimination rate constant (Ke) 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.
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Jinglei Du, Lin Zhu, Xue Zhou, Wei Yin, Aifang Deng, Jinping Qiao,