分类号：R945R99-第三军医大学学报.DOC

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 Release Study in vivo of Methotrexate Modified by LHRH Zhang Yarong, Zeng Li, Wu Xueping, Wang Chi (College of Pharmacy,Chongqing Medical University ,Chongqing, 400016,China) [Abstract] Objective To study the vivo release of MTX from LHRH-MTX in model animals. Methods A HPLC method was established to determine the concentrations of drugs in plasma and other tissues o f the tumor-bearing nude mice after an intravenous administration. Compared with MTX injection, the capacity of the vivo release of MTX from LHRH-MTX was evaluated. Results The recoveries of the established method were more than 85%, and the relative standard deviations of the intra-day and inter-day were less than 10%. Afeter an administration,the concentrations of MTX from LHRH-MTX were higher in tumor tissues（P0.05）, but lower in plasma, liver and kidney（P0.05）. Conclusion The established HPLC method is easy to be used in the vivo release of LHRH-MTX study . LHRH-MTX significantly changed the distribution of MTX in vivo and evidently increased the concentrations of MTX in tumor tissues . [Key words] methotrexate; luteinizing hormone-releasing hormone; HPLC; in vivo release Supported by the Planning Project of Science and Technology of Yuzhong District,Chongqing ..Corresponding author:Wang Chi,Tel:86-23E-mail: wchi639@ 甲氨蝶呤(Methotrexate，MTX)属于二氢叶酸还原酶抑制剂, 是目前临床常用的抗代谢类抗恶性肿瘤药物主要用于头颈部癌、肺癌、各种软组织肉瘤、乳腺癌、卵巢癌、绒毛膜上皮癌等肿瘤的治疗，MTX对肿瘤同时也对正常组织产生毒性作用MTX等化疗药物用于肿瘤治疗中常遇到的问题。随着对肿瘤研究的不断深入，在肿瘤细胞表面发现了受体，它们与肿瘤的生长和增殖密切相关，且在肿瘤组织中表达，促黄体释放激素受体、生长