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.
作者
张韫琪
张仕畅
赵怡伟
赵博欣
蔡素芬
李国锋
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)
出处
《今日药学》
CAS
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)。