Determination of 6258-70,a new semi-synthetic taxane,in rat plasma and tissues:Application to the pharmacokinetics and tissue distribution study

作     者：Simin Zhao Yuanyuan Zhang Ping Ju Liqiang Gu Rui Zhuang Longshan Zhao Xing Tang Kaishun Bi Xiaohui Chen 

作者机构：School of PharmacyShenyang Pharmaceutical University 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2016年第6卷第4期

页      面：219-225页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 10[医学] 100602[医学-中西医结合临床] 0702[理学-物理学] 

主　　题：6258 70 HPLC MS/MS Pharmacokinetics Tissue distribution 

摘      要：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.