HPLC-MS法分析甲苯磺酸拉帕替尼中痕量基因毒性杂质

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,5 μm),以0.1%甲酸溶液-乙腈(20:80)为流动相,流速1.0 mL · min^-1,电喷雾离子化(ESI)正离子模式下选择m/z 252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 · mL^-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 LC-MS analytical method for the determination of genotoxic impurity in lapatinib ditosylate. Methods: The analytical column was C₁₈ (4.6 mm×250 mm, 5 μm), the mobile phase was 0.1% formic acid-acetonitrile (20:80), and the flow rate was 1.0 mL · min^-1.The detection was achieved in ESI positive ion mode with m/z 252 ion. Results: The calibration curve of genotoxic impurity was in a good linearity over the range of 0.08-8 ng · mL^-1 (r=1.000).The limit of detection was 0.0036 ng, and the limit of quantification was 0.0107 ng.Repetition of genotoxic impurity was fine, with RSD (n=6) of 7.5%.Recovery (n=9) of the genotoxic impurity was 96.6%. Conclusion: The method is simple, rapid and reliable, which is applicable for the quality control of genotoxic impurity in lapatinib ditosylate.

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