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FK-3000 can inhibit proliferation of carcinomas and arrest the growth of carcinoma cells through cytotoxic (apoptosis induction) and cytostatic (cell cycle arrest) effects. A rapid and sensitive assay was developed and validated using liquid chromatography-mass spectrometry (LC-MS) for FK-3000 in rat plasma. FK-3000 was extracted with ethyl acetate from rat plasma samples, and the residue containing the FK-3000 was dried in a gentle stream of nitrogen and reconstituted with acetonitrile. The FK-3000 was quantified using high-performance liquid chromatography (HPLC; Waters Alliance 2695) with a reversed phase Gemini column (3 mm × 150 mm, 5 μm; Phenomenex, USA) and a Waters Micromass ZQ detector. FK-3000 and phenazine, an internal standard (IS), were analyzed by selected ion monitoring (SIM) at m/z transitions of 418.45 and 256, respectively. A lower limit of quantification (LLOQ) of 10 ng/mL was observed, with a linear dynamic range from 10 to 10,000 ng/mL (R>0.999). The accuracy, precision, recovery, matrix effects, and stability of the assay were deemed acceptable according to the FDA guidance for industry (bioanalytical method validation). The FK-3000 concentration was measured in plasma samples up to 6 h following FK-3000 administration at an oral dose of 20 mg/kg. The findings indicate that the assay method is suitable for routine pharmacokinetic (PK) studies of FK-3000 in rats. Copyright © 2012 Elsevier B.V. All rights reserved.


Jong-Hwa Lee, Yoon-Jee Chae, Kyeong-Ryoon Lee, Sung-Hoon Ahn, Joung-Wook Seo, Qing-Ri Jin, Young-Ah Woo, Gye-Won Lee, Soon-Chang Cho, Sung-Won Kwon, Dae-Hun Park. Development of a LC-MS method for quantification of FK-3000 and its application to in vivo pharmacokinetic study in drug development. Journal of pharmaceutical and biomedical analysis. 2012 Nov;70:587-91

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PMID: 22738786

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