阿霉素纳米胶束在大鼠体内的组织分布研究  

Tissue distribution research on adriamycin nanometer micelles in rats

作　　者：陈思明[1,2] 徐海燕[2] 乔明曦[2] 索昊[2] 李志远 袁波 CHEN Siming;XU Haiyan;QIAO Mingxi;SUO Hao;LI Zhiyuan;YUAN Bo(Hainan Wuzhishan Branch of Food and Drug Administration,Wuzhishan 572200,China;Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]海南省食品药品检验所五指山分所,五指山572200 [2]沈阳药科大学,沈阳110016

出　　处：《西北药学杂志》2019年第2期194-198,共5页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:30801456)

摘　　要：目的建立大鼠组织样品的预处理及液相色谱-串联质谱(LC-MS/MS)测定方法,测定阿霉素纳米胶束和阿霉素注射液在大鼠体内的组织分布。方法采用甲醇∶生理盐水(4∶1)作为组织匀浆介质;色谱柱:SunFire C_(18)(250 mm×4.6 mm,5μm);流动相:5 mmol·L^(-1)醋酸铵-乙腈-甲酸(70∶30∶0.5);流速:0.5 mL·min^(-1);对乙酰氨基酚作为内标。在此色谱条件下,以多反应监测(MRM)扫描方式进行检测,将大鼠随机分成2组,分别测定大鼠尾静脉注射阿霉素纳米胶束和阿霉素注射液后各组织中阿霉素的药物质量浓度,给药剂量均为1 mg·kg^(-1)。结果大鼠各组织中阿霉素的质量浓度在0.5～200 ng·mL^(-1)范围内线性关系良好,r=0.999 1,样品的日内精密度RSD值小于6.7%,日间精密度RSD值小于13.2%。结论该方法快速、准确,适用于阿霉素在大鼠体内组织分布的研究,阿霉素纳米胶束与阿霉素注射液在心、脾和肺中的分布差异无统计学意义,在肝和肾中的分布差异有统计学意义,2种制剂均不能透过血脑屏障。Objective To establish a method for the determination of adriamycin nanomicelles and adriamycin injection in rat tissues by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Methods Using methanol-physiological saline (4∶1) as the tissue sample homogenate medium,the separation was performed on a reversed-phase SunFire C 18 column (250 mm×4.6 mm,5 μm).The mobile phase was consisted of 5 mmol·L^-1 ammonium acetate-acetonitrile-formic acid (70∶30∶0.5),the flow rate:0.5 mL·min^-1 .The internal standard substance was paracetamol.Under the chromatographic conditions,the detection was carried out by multiple reaction monitoring (MRM).Rats were divided into 2 groups at random.Adriamycin nano micelles and adriamycin injection were used in rats by caudal vein injection with 1 mg·kg^-1 respectively.Results The method had a linear calibration curve over the range of 0.5-200 ng·mL^-1 ( r =0.999 1).The intra-day precision RSD were within 6.7% and inter-day precision RSD were within 13.2% for the analyte.Conclusion The proposed analytic method is rapid,sensitive,and can be applied for the identification and quantification in tissue distribution studies of adriamycin in rats.The distribution of adriamycin nano micelles and adriamycin injection in heart,spleen and lung showed no significant difference,but showed significant differences in the liver and kidney.Both preparations could not penetrate the blood-brain barrier.

关 键 词：阿霉素 液相色谱-串联质谱(LC-MS/MS)法 组织分布 

分 类 号：R965[医药卫生—药理学]