LC-MS/MS法测定遗传毒性杂质9-丙烯基腺嘌呤  

Determination of 9-Propenyladenine by LC-MS/MS

作　　者：王秀珍 张治云 宋永保 杨海霞 WANG Xiu-zhen;ZHANG Zhi-yun;SONG Yong-bao;YANG Hai-xia(Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China;Shandong Provincial Key Laboratory of Chemical Drugs,Jinan 250101,China;Shandong Haiyou Freda Pharmaceutical Co.,Ltd.,Linyi 276700,China)

机构地区：[1]山东省药学科学院,山东济南250101 [2]山东省化学药物重点实验室,山东济南250101 [3]山东海佑福瑞达制药有限公司,山东临沂276700

出　　处：《食品与药品》2018年第1期28-31,共4页Food and Drug

摘　　要：目的建立富马酸替诺福韦二吡呋酯中痕量遗传毒性杂质9-丙烯基腺嘌呤含量测定方法。方法采用高效液相色谱-串联质谱(LC-MS/MS)技术,以C_(18)柱分离,乙腈-10 mmol/L乙酸铵溶液(35:65,v/v)为流动相,流速为1.0 ml/min。用正离子扫描方式检测,多反应监测(MRM)模式扫描,检测离子通道为m/z:176.1/136.1。结果 9-丙烯基腺嘌呤浓度在0.49~24.50 ng/ml范围内与峰面积呈良好线性关系,相关系数为0.9999;定量限为0.49 ng/ml;平均加样回收率为99.18%,RSD为2.78%(n=9);对照品溶液连续进样6次,峰面积RSD为1.72%。结论本方法专属性强、灵敏度高、准确度好,可用于富马酸替诺福韦二吡呋酯中9-丙烯基腺嘌呤的含量测定。Objective To establish a method for the determination of 9-propenyladenine which is a trace genotoxic impurity in tenofovir disoproxil fumarate.Methods 9-Propenyladenine was separated and determined by LC-MS/MS.It was separated on a C18 column with acetonitrile-10 mmol/L ammonium acetate solution(35:65,v/v)as the mobile phase.The flow rate was 1.0 ml/min.The detection was accomplished by tandem mass spectroscopy in the positive ion multiple reaction monitoring(MRM)mode with ion transitions of m/z 176.1/136.1.Results The standard curve was linear in the range of 0.49-24.50 ng/ml(r=0.9999)for 9-propenyladenine and the limit of quantification was 0.49 ng/ml.The average recovery was 99.18%with RSD of 2.78%(n=9).The RSD of precision(n=6)was 1.72%.Conclusion The method can be accurate,sensitive and specific,and can be used for the determination of trace genotoxic impurity 9-propenyladenine in tenofovir disoproxil fumarate.

关 键 词：替诺福韦二吡呋酯 遗传毒性杂质 9-丙烯基腺嘌呤 高效液相色谱-串联质谱 

分 类 号：R927.2[医药卫生—药学]