Shi Huiyan, Hou Chenzhi, Gu Liqiang, Wei Zhe, Xing Hang, Zhang Meiyu, Wang Shixiao, Zhao Longshan, Bi Kaishun, Chen Xiaohui
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
Asian J Pharm Sci. 2017 Mar;12(2):202-208. doi: 10.1016/j.ajps.2016.08.010. Epub 2016 Sep 21.
The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats. A simple and efficient high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) method was developed to determine methotrexate in rat plasma. Methotrexate and syringic acid (internal standard) were extracted from rat plasma samples by protein precipitation with acetonitrile. The analysis was performed on a CAPCELL PAK C column (150 mm × 4.6 mm, 5 µm) with acetonitrile and 5 mmol/l ammonium acetate aqueous (10:90, ). The linear range was 5.0 × 10 to 100.0 µg/ml for methotrexate. Other parameters were all within the acceptance criteria. The validated method was successfully applied the pharmacokinetic study of methotrexate between two methotrexate treated groups (with and without the pretreatment of piperazine ferulate). Compared with the methotrexate treated alone group, the pharmacokinetic parameters in the methotrexate with the pretreatment of piperazine ferulate group showed significantly lower MRT, MRT and . Results suggested that methotrexate can be rapidly eliminated, cleared or metabolized in rat blood, which might be related to the pretreatment of piperazine ferulate. The method provided deeper insights into rational clinical use of methotrexate with the pretreatment of piperazine ferulate on cancer patients with renal dysfunction.
本研究旨在探讨阿魏酸哌嗪预处理对甲氨蝶呤致肾损伤大鼠甲氨蝶呤药代动力学参数的影响。建立了一种简单高效的高效液相色谱-质谱联用（HPLC-MS）方法测定大鼠血浆中甲氨蝶呤的含量。采用乙腈蛋白沉淀法从大鼠血浆样品中提取甲氨蝶呤和丁香酸（内标）。分析在CAPCELL PAK C柱（150 mm × 4.6 mm，5 µm）上进行，流动相为乙腈和5 mmol/l醋酸铵水溶液（10:90）。甲氨蝶呤的线性范围为5.0×10至100.0 µg/ml。其他参数均在可接受标准范围内。该验证方法成功应用于两个甲氨蝶呤治疗组（有或无阿魏酸哌嗪预处理）的甲氨蝶呤药代动力学研究。与单独使用甲氨蝶呤治疗组相比，阿魏酸哌嗪预处理的甲氨蝶呤组药代动力学参数显示MRT、MRT和显著降低。结果表明，甲氨蝶呤在大鼠血液中可快速消除、清除或代谢，这可能与阿魏酸哌嗪预处理有关。该方法为阿魏酸哌嗪预处理甲氨蝶呤在肾功能不全癌症患者中的合理临床应用提供了更深入的见解。
