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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 C_(18) column(50 mm × 2.1 mm,2.6 μm,Phenomenex,USA) within3 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.
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 C 18 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 %. And 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 indic ated 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. 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.