LC-MS/MS法测定遗传毒性杂质4-(3-氟苯甲氧基)-3-氯苯胺

摘要

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, 5 μm) 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.%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C8色谱柱(4.6 mm×250 mm,5 μm),以水(A)-甲醇(B)为流动相,采用梯度洗脱(0～3 min,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.