Zhao Simin, Zhang Yuanyuan, Ju Ping, Gu Liqiang, Zhuang Rui, Zhao Longshan, Tang Xing, Bi Kaishun, Chen Xiaohui
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
J Pharm Anal. 2016 Aug;6(4):219-225. doi: 10.1016/j.jpha.2016.02.003. Epub 2016 Mar 2.
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 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.
癌症是全球主要的死亡原因。在化疗药物中，紫杉烷类在癌症治疗中发挥着重要作用。6258 - 70是一种新型半合成紫杉烷，具有广泛的抗肿瘤活性。本文建立了一种快速可靠的高效液相色谱 - 串联质谱法（HPLC - MS/MS），用于定量大鼠血浆和组织中的6258 - 70。采用甲基叔丁基醚液 - 液萃取法提取后，样品在Kinetex C柱（50 mm×2.1 mm，2.6 µm，美国菲罗门公司）上3分钟内实现分离。该方法经过充分验证，基质效应在87.7%至99.5%之间，回收率在80.3%至90.1%之间。日内和日间精密度均小于9.5%，准确度在 - 3.8%至6.5%之间。该可靠方法成功应用于大鼠静脉注射6258 - 70后的药代动力学和组织分布研究。药代动力学结果表明，在1至4 mg/kg的测试剂量范围内，6258 - 70在大鼠体内的药代动力学行为符合线性特征，且两性之间无显著差异。组织分布研究表明，6258 - 70具有有效渗透性，广泛且快速扩散，并可穿越血脑屏障。药代动力学和组织分布结果可为未来研究提供指导。
