促黄体激素释放激素修饰的甲氨蝶呤体内释放研究.docVIP

促黄体激素释放激素修饰的甲氨蝶呤体内释放研究( 张雅溶，曾 理，吴学萍，王 驰 （400016 重庆，重庆医科大学药学院药物化学教研室） [摘要] 目的 研究促黄体释放激素(LHRH-MTX)在模型动物体内释放MTX情况。方法 建立HPLC的分析方法，经尾静脉注射给药，测定荷瘤裸鼠血液和组织中的药物浓度；与MTX制剂比较，评价LHRH-MTX在体内释放MTX情况。结果 建立的HPLC分析方法回收率高于85%，日间和日内精密度（RSD）均小于10%，符合生物样品分析要求；静脉注射给药后，经统计学分析，与MTX制剂相比，LHRH-MTX释放的MTX在血液、肝脏、肾脏的浓度有明显下降（P0.05）（P0.05）HPLC用于LHRH-MTX体内释放研究结果良好，LHRH-MTX释药后MTX在体内的组织分布有明显的改变，在肿瘤部位有明显的浓集。 [关键词] 甲氨蝶呤；促黄体激素释放激素；高效液相色谱法；体内释放 [中图法分类号] [文献标志码] A In vivo release study of methotrexate modified by luteinizing hormone- releasing hormone Zhang Yarong, Zeng Li, Wu Xueping, Wang Chi (Department of Pharmaceutical chemistry, College of Pharmacy, Chongqing Medical University, Chongqing,, 400016, China) [Abstract] Objective To study the in vivo release of methotrexate (MTX) from luteinizing hormone- releasing hormone (LHRH) modified MTX in model animals. Methods A total of 60 nude Balb/c mice received a subcutaneous injection of MCF-7 cells, and 50 of them with tuore mass in size of 1.5 cm served as model animals. These mice were further divided into 2 groups, and received an injection of 10 mg/kg MTX and 28 mg/kg MTX-LHRH respectively by tail vein. Then the animals were killed at 1, 2, 4, 12 and 24 h after injection (5 mice at each time points), and their blood and heart, liver, spleen, kidney and tumor mass were collected. A HPLC method was established to determine the concentrations of drugs in the plasma and other tissues of the tumor-bearing nude mice. Compared with MTX injection, the capacity of the in vivo release of MTX from LHRH-MTX was evaluated. Results The recoveries of our established HPLC method were more than 85%, and the relative standard deviations of the intra-day and inter-day were lesser than 10%. After venous administration, the concentrations of MTX from LHRH-MTX were higher in tumor tissues（P0.05）, but lower in the plasma, liver and kidney（P0.05）. Conclusion Our established HPLC method is easy to determine the in vivo release of LHRH-MT