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目的:建立液相色谱-质谱联用方法测定甲苯磺酸拉帕替尼中基因毒性杂质的含量。方法:采用色谱柱C18(4.6 mm×250 mm,5μm),以0.1%甲酸溶液-乙腈(20∶80)为流动相,流速1.0 m L·min-1,电喷雾离子化(ESI)正离子模式下选择m/z252离子进行检测。结果:基因毒性杂质4-(3-氟苯甲氧基)-3-氯苯胺质量浓度在0.08~8 ng·m L-1范围内,与峰面积线性关系良好(r=1.000);检测限为0.003 6 ng,定量限为0.010 7 ng;样品中基因毒性杂质测定结果的重复性良好,RSD(n=6)为7.5%;基因毒性杂质平均回收率(n=9)为96.6%。结论:本方法操作简便,结果可靠,可以用于甲苯磺酸拉帕替尼中基因毒性杂质4-(3-氟苯甲氧基)-3-氯苯胺含量的检测。
Objective: To establish a method for the determination of genotoxic impurities in lapatinib tosylate by liquid chromatography-mass spectrometry. Methods: The mobile phase of C18 (4.6 mm × 250 mm, 5 μm) with 0.1% formic acid and acetonitrile (20:80) was used as the mobile phase at a flow rate of 1.0 mL · min -1. Electrospray ionization (ESI) Mode to select m / z252 ions for testing. Results: The mass concentration of genotoxic impurity 4- (3-fluorobenzyloxy) -3-chloroaniline was in the range of 0.08-8 ng · m L-1, with a good linear relationship with the peak area (r = 1.000) Was 0.003 6 ng, with a limit of quantification of 0.010 7 ng. The reproducibility of genotoxic impurities in the samples was good with RSD (n = 6) of 7.5% and the average recovery of genotoxic impurities was 96.6% (n = 9). Conclusion: The method is simple, reliable and can be used to detect genotoxicity of 4- (3-fluorobenzyloxy) -3-chloroaniline in lapatinib tosylate.