determination of 6258-70, a new semi-synthetic taxane, in rat plasma and tissues: application to the pharmacokinetics and tissue distribution study
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ID: 239851
2016
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Abstract
Cancer is the leading cause of death all over the world. Among the chemotherapy drugs, taxanes play an important role in cancer treatment. 6258-70 is a new semi-synthetic taxane which has a broad spectrum of antitumor activity. A fast and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) method was developed for quantification of 6258-70 in rat plasma and tissues in this paper. After extraction by liquid-liquid extraction method with methyl tert-butyl ether, the samples were separated on a Kinetex C18 column (50 mm×2.1 mm, 2.6 µm, Phenomenex, USA) within 3 min. The method was fully validated with the matrix effect between 87.7% and 99.5% and the recovery ranging from 80.3% to 90.1%. The intra- and inter-day precisions were less than 9.5% and the accuracy ranged from −3.8% to 6.5%. The reliable method was successfully applied to the pharmacokinetics and tissue distribution studies of 6258-70 after intravenous administration in rats. The pharmacokinetic results indicated that the pharmacokinetic behavior of 6258-70 in rats was in accordance with linear features within tested dosage of 1 to 4 mg/kg, and there was no significant difference between the two genders. The tissue distribution study showed that 6258-70 had an effective penetration, spread widely and rapidly and could cross blood-brain barrier. The results of pharmacokinetics and tissue distribution may provide a guide for future study.
| Reference Key |
zhao2016journaldetermination
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|---|---|
| Authors | ;Simin Zhao;Yuanyuan Zhang;Ping Ju;Liqiang Gu;Rui Zhuang;Longshan Zhao;Xing Tang;Kaishun Bi;Xiaohui Chen |
| Journal | Frontiers in plant science |
| Year | 2016 |
| DOI |
10.1016/j.jpha.2016.02.003
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