嘧啶核苷类化合物GY005对小鼠的急性毒性试验和在大鼠体内的粪尿排泄实验研究  

Acute toxicity test of the pyrimidine nucleoside GY005 on Mice and its excretion in rats

作　　者：陶乐[1] 李玉江[1] 路博华 梁炳玉 彭有梅 郭晓河[1] 董黎红[1] TAO Le;LI Yujiang;LU Bohua;LIANG Bingyu;PENG Youmei;GUO Xiaohe;DONG Lihong(High&New Technology Research Center of Henan Academy of Sciences,Zhengzhou 450002,Henan,China;Institute of Medical and Pharmaceutical Sciences,Zhengzhou Unirersity,Zhengzhou 450001,Henan,China)

机构地区：[1]河南省科学院高新技术研究中心,河南郑州450002 [2]郑州大学河南省医药科学研究院,河南郑州450001

出　　处：《化学研究》2025年第1期73-78,共6页Chemical Research

基　　金：河南省重点研发专项项目(241111314100);河南省科技创新杰出青年基金资助项目(094100510019);河南省科技攻关计划项目(232102310380);河南省科学院基本科研费项目(230602007);河南省理化分析测试工程技术中心运行费项目(241002036)。

摘　　要：采用最大给药量法进行嘧啶核苷类化合物GY005对KM小鼠的急性毒性试验;建立LC-MS/MS法测定大鼠尿液和粪便中化合物GY005的浓度,研究其在大鼠体内的排泄行为。每个时间段的尿液样本通过量筒量得体积并记录,粪便收集后立即称重得到样本湿重并记录,样品置于-80℃待测,选用特非那定作为内标检测。结果显示,一次给小鼠经口灌服化合物GY005(5.0 g·kg^(-1)),所有动物均未发现明显的毒性反应;化合物GY005在4~4000μg·L^(-1)与峰面积线性关系良好,所建立方法简单易操作、准确性好、精密度高,提取回收率、基质效应和稳定性也符合要求。The maximum dose method was used to perform the acute toxicity test of nucleoside analogue GY005 on KM mice;a LC-MS/MS method for determination of nucleoside analogue GY005 in rat urine and feces was established and its excretion behavior in rats was studied.The volume of urine samples at each time period was measured and recorded using a cylinder.The wet weight of fecal collection was immediately weighed and recorded.The samples were placed at-80°C,and terfenadine was selected as the internal standard.The experimental results showed that no significant toxic reactions were found in any animal after nucleoside analogue GY005(5.0 g·kg^(-1))was orally administered to mice and nucleoside analogue GY005 had a good linear relationship with peak area between 4 and 4000μg·L^(-1).The established method was simple and easy to operate,with high accuracy and precision,extraction recovery rate,matrix effect,and stability met the requirements.

关 键 词：核苷类化合物 急性毒性 尿 粪 排泄 

分 类 号：R969.1[医药卫生—药理学]