LC-MS/MS法检测大鼠血浆和各组织中阿霉素含量  

Determination of Adriamycin in Rat Plasma and Tissues by LC-MS/MS

作　　者：张韫琪 张仕畅 赵怡伟 赵博欣[2,3] 蔡素芬 李国锋[2,3,4] ZHANG Yunqi;ZHANG Shichang;ZHAO Yiwei;ZHAO Boxin;CAI Sufen;LI Guofeng(Guangzhou Institute of Dermatology,Guangzhou,Guangdong 510030,China;Department of Pharmacy,Nanfang Hospital,Southern Medical University,Guangzhou.,Guangdong 510515,China;Laboratory of Rational Drug Use Evaluation and Drug Delivery Development,Nanfang Hospital,Southern Medical University,Guangzhou.,Guangdong 510515,China;Guangdong Key Laboratory for New Drug Screening,School of Pharmacy,Southern Medical University,Guangzhou,Guangdong 510515,China)

机构地区：[1]广州市皮肤病研究所,广东广州510030 [2]南方医科大学南方医院药学部,广东广州510515 [3]南方医科大学南方医院合理用药评价与药物递送发展实验室,广东广州510515 [4]南方医科大学药学院,广东省新药筛选重点实验室,广东广州510515

出　　处：《今日药学》2021年第10期748-752,共5页Pharmacy Today

基　　金：广州市科技计划项目(201804010065);广东省基础与应用基础研究基金项目(2020A1515010396);广州市皮肤病防治所医药卫生科技项目(202003)。

摘　　要：目的建立液相色谱-质谱联用(LC-MS/MS)测定大鼠血浆和心、肝、肺、肾、脑组织中阿霉素的方法。方法样本经乙腈-5 mmol·L^(-1)乙酸铵(60∶40,V/V)提取淀蛋白,C_(18)色谱柱分离,含0.1%甲酸的乙腈和0.1%甲酸水溶液,采用柱后分流模式梯度洗脱,以柔红霉素作为内标,在电喷雾离子化(ESI)正离子模式下检测,多反应监测(MRM)扫描,用于定量的离子对分别为544.2→m/z 397.2(阿霉素)和m/z 528.2→m/z 321.2(柔红霉素,内标)。结果阿霉素在血浆浓度5~2000 ng·mL^(-1),在心脏组织浓度10~4000 ng·mL^(-1),在肝组织浓度10~4000 ng·mL^(-1),在肺组织浓度10~4000 ng·mL^(-1),在肾组织浓度5~4000 ng·mL^(-1),在脑组织浓度1~2000 ng·mL^(-1)范围内与峰面积有良好的线性关系,相关系数分别为0.999,0.997,0.992,0.991,0.998,0.994。血浆和各组织方法提取回收率均在78.5%~101.2%,日内及日间精密度的RSD<15%。介质效应在89%~115%之间。结论此方法专属性强、检测限低、操作简单、快速,适用于动物血浆和组织中阿霉素残留浓度的检测。OBJECTIVE To establish a LC-MS/MS method for the determination of adriamycin in plasma,heart,liver,lung,kidney and brain tissues.METHODS The samples were extracted by acetonitrile-5 mmol·L^(-1) ammonium acetate(60∶40,V/V)and separated by C_(18) column.The mobile phases were consisted of cetonitrile containing 0.1%formic acid and water containing 0.1%formic acid.The gradient elution was used in post-column shunt mode.Daunorubicin was used as the internal standard and detected under the electrospray ionization(ESI)cation mode.m/z 544.2→m/z 397.2(adriamycin)and m/z 528.2→m/z 321.2(daunorubicin,internal standard)were quantitated by multiple reaction monitoring(MRM).RESULTS There had a good linear relationship with peak area in the concentration range of 5-2000 ng·mL^(-1) in plasma,10-4000 ng·mL^(-1) in heart,10-4000 ng·mL^(-1) in liver,10-4000 ng·mL^(-1) in lung,5-4000 ng·mL^(-1) in kidney and 1-2000 ng·mL^(-1) in brain.The correlation coefficients were 0.999,0.997,0.992,0.991,0.998 and 0.994,respectively.The recoveries of adriamycin in plasma and tissues extraction ranged from 78.5%-101.2%.RSD of intra day and inter day precision were less than 15%.The dielectric effect was between 89%-115%.CONCLUSION This method have the advantages of high specificity,low detection limit,simple and rapid operation,and is suitable for the determination of residual adriamycin in animal plasma and tissues.

关 键 词：阿霉素 LC-MS/MS 血浆 心组织 肝组织 肺组织 肾组织 脑组织 浓度 

分 类 号：R917[医药卫生—药物分析学]