Zheng Jian, Shao Changmin, Fan Bo, Jing Lijia, Li Siyang, Yan Xiufeng, Wang Yang
Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education/Center for Bioactive Products, Northeast Forestry University, Harbin, Heilongjiang, China.
Jiangsu Food & Pharmaceutical Science College, Huaian, Jiangsu, China.
Biomed Chromatogr. 2018 Nov;32(11):e4336. doi: 10.1002/bmc.4336. Epub 2018 Aug 19.
In the present study, a 10-position modified of camptothecin, 10-propionyloxy camptothecin (PCPT) was esterified from 10-hydroxcamptothecin (HCPT), which could metabolize to HCPT in vivo. PCPT displayed a relatively stronger antitumor activity in vitro and in vivo. Thereafter a simple, sensitive and rapid HPLC method coupled with a fluorescence detector was developed and validated for the assay of PCPT and its active metabolite HCPT in rat plasma. The method was validated for accuracy, precision, linearity, selectivity and recovery. The validated method was successfully applied to the pharmacokinetic study of PCPT in rats after intravenous administration. The results showed that PCPT could be mainly converted to HCPT in plasma with the AUC value of 3.69 ± 4.44 and 311.16 ± 188.81 ng h/mL for PCPT and HCPT, respectively.
在本研究中，喜树碱的10位修饰物10-丙酰氧基喜树碱（PCPT）由10-羟基喜树碱（HCPT）酯化得到，其在体内可代谢为HCPT。PCPT在体外和体内均表现出相对较强的抗肿瘤活性。此后，建立了一种简单、灵敏、快速的高效液相色谱法，该方法配备荧光检测器，用于测定大鼠血浆中PCPT及其活性代谢物HCPT，并进行了方法验证。该方法在准确性、精密度、线性、选择性和回收率方面得到了验证。经过验证的方法成功应用于大鼠静脉注射PCPT后的药代动力学研究。结果表明，PCPT在血浆中主要转化为HCPT，PCPT和HCPT的AUC值分别为3.69±4.44和311.16±188.81 ng h/mL。
