硝胺推进剂在大鼠体内代谢动力学及病理学研究  

Pharmacokinetics and pathologies of missile propulsion nitramines in rats

作　　者：张茜[1] 李鹏飞[2] 吕亚丽[2] 安卓玲[2] 吴诚[3] 李广润[2] 刘丽宏[2] 

机构地区：[1]湖北中医药大学药学院,湖北武汉430065 [2]首都医科大学附属朝阳医院药事部,北京100020 [3]第二炮兵总医院药学部,北京100088

出　　处：《国际检验医学杂志》2013年第3期263-265,268,共4页International Journal of Laboratory Medicine

摘　　要：目的研究推进剂中硝基胺类化合物在大鼠体内的吸收、分布和消除过程,并对单次尾静脉注射小剂量硝基胺类化合物后8h大鼠病理组织学进行了考察。方法大鼠尾静脉注射黑索金和奥克托金混合水溶液,用高效液相串联质谱法测定血浆中的硝基胺类化合物浓度,浓度-时间数据用DAS2.0软件进行分析,计算药动学参数;考察给药组及空白组肝脏肾脏ALT、ALP、AST指标变化;给药后8h大鼠颈椎脱臼处死,解剖取肝脏肾脏进行病理学组织考察。结果大鼠尾静脉注射0.5mL硝基胺类化合物混合水溶液后,RDX的t1/2为(324.68±188.91)min,Cmax为(127.50±28.39)ng/mL,AUC0-t为(24164.75±5401.43)ng·min-1·mL-1;HMX的t1/2为(134.88±100.01)min,Cmax为(26.78±7.82)ng/mL,AUC0-t为(3787.55±2587.03)ng·min-1·mL-1;给药组与空白组相比,大鼠肝脏肾脏指标ALT和AST有升高趋势;尾静脉注射8h后大鼠肠胀气严重,但肝脏肾脏组织均未见病理变化。结论 RDX和HMX在血液中分布比例小,两者消除速率没有显著差异,注射硝胺化合物对大鼠肝脏肾脏指标有一定影响,但无病理组织学变化。Objective To study the pharmacokinetics of nitramines in rats and the ratsf pathological changes after being injected a single dose nitramine compounds intravenously. Methods Rats were given a single dose of nitramine compounds intravenously and plasma samples were collected. The concentrations of RDX and HMX in plasma were detected by LC-MS/MS. Pharmaeokinet- ics parameters were determined from the plasma concentration- time data with the DAS 2.0 software. The ALT,ALP and AST in plasma were also detected,and the rats pathologies of nitramines were investigated after been sacrificed. Results After intravenous administration of nitramines, t1/2 values of RDX and HMX were respectively （324. 68± 188.91 ） min and （ 134.88 ± 100. 01 ） min, reaching Cmax of （127. 50 ± 28. 39） ng/mL of RDX and （26. 78 ± 7. 82） ng/mL of HMX, and their AUC0-t were（24 164. 75 ± 5 401.43）ng · min^-1 · mL ^-1 and（3 787.55±2 587.03）ng · min^-1 · mL^-1 ,respectively. Conclusion RDX and HMX could be ab- sorbed rapidly after intravenous administration, but only a very small part of them could be distributed in the blood. There might be no difference on the eliminate rate of the two nitramines. Abnormalities could be observed in the liver and kidney indices of the rats after intravenous administration, but no pathological changes could be found.

关 键 词：硝基胺类化合物 毒物代谢动力学 液相色谱串联质谱 

分 类 号：R114[医药卫生—卫生毒理学]