LC-MS/MS法测定遗传毒性杂质4-(3-氟苯甲氧基)-3-氯苯胺  

Determination of Genotoxic Impurity 4-(3-fluorophenyl-methoxy)-3-chloroaniline by LCMS/MS

作　　者：王秀珍 王帆 王洪臣 杨海霞 WANG Xiu-zhen;WANG Fan;WANG Hong-chen;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2期102-105,共4页Food and Drug

摘　　要：目的建立液质联用方法测定甲苯磺酸拉帕替尼及片中遗传毒性杂质4-(3-氟苯甲氧基)-3-氯苯胺的含量。方法采用C_8色谱柱(4.6 mm×250 mm,5μm),以水(A)-甲醇(B)为流动相,采用梯度洗脱(0~3min,40%B→90%B;3~8 min,90%B→95%B),流速0.7 ml/min,柱温30℃;ESI离子源,正离子扫描方式,多反应监测(MRM)模式扫描,检测离子通道为m/z:252.1→143.1。结果 4-(3-氟苯甲氧基)-3-氯苯胺浓度在0.24~103.89 ng/ml范围内与峰面积呈良好线性关系(r=0.9996);定量限为0.24 ng/ml;检出限为0.072 ng/ml;平均加样回收率为100.98%,RSD为2.58%(n=9)。结论本方法专属性强、灵敏度高、准确度好,可用于甲苯磺酸拉帕替尼及片中杂质4-(3-氟苯甲氧基)-3-氯苯胺的测定。Objective To establish a LC-MS/MS method for the determination of 4-(3-fluorophenyl-methoxy)-3-chloroaniline which is a genotoxic impurity in lapatinib ditosylate API and tablets.Methods 4-(3-fluorophenylmethoxy)-3-chloroaniline was separated on a C8 column(4.6 mm×250 mm,5μm)and the column temperature was 30℃.The mobile phase consisted of water(A)-methanol(B)with a gradient elution(0-3 min,40%B→90%B;3-8 min,90%B→95%B)at a flow rate of 0.7 ml/min.It was detected by tandem mass spectroscopy in the positive ion multiple reaction monitoring(MRM)mode with ion transitions of m/z:252.1→143.1.Results The calibration curve of 4-(3-fluorophenyl-methoxy)-3-chloroaniline was in a good linearity over the range of 0.24-103.89 ng/ml(r=0.9996).The limit of quantification was 0.24 ng/ml and the limit of detection was 0.072 ng/ml.The average recovery was 100.98%and RSD was 2.58%(n=9).Conclusion The method can be accurate,sensitive and specific,and can be used for the determination of 4-(3-fluorophenyl-methoxy)-3-chloroaniline in lapatinib ditosylate.

关 键 词：甲苯磺酸拉帕替尼 4-(3-氟苯甲氧基)-3-氯苯胺 高效液相色谱-质谱联用 痕量杂质检测 

分 类 号：R927[医药卫生—药学]