盐酸厄洛替尼基因毒性杂质液相色谱-质谱联用分析方法学验证

建立了一种液相色谱-质谱联用法对盐酸厄洛替尼片中基因毒性杂质3-乙炔苯胺含量的测定方法。采用ESI离子源正离子多反应监测（MRM）模式，选择离子对118→75、118→91进行测定。色谱柱为Thermo Hypersil GOLD C8（100 mm×4.6 mm，3 μm），流动相为甲醇和水，梯度洗脱，流速为0.4 mL/min，柱温为35℃。结果表明：该方法中3-乙炔苯胺的检测质量浓度在1.0～20 ng/mL 的范围内呈良好的线性关系，R²= 0.999 4；精密度实验的相对标准偏差（n=6）为1.13%，低、中、高浓度的加标回收率（n=3）为90.1%～106.1%。该方法灵敏度高、专属性好、精密度高，满足盐酸厄洛替尼片中基因毒性杂质3 乙炔苯胺含量的测定要求。

Methodology validation for the analysis of genotoxic impurity in erlotinibhydrochloride with liquid chromatography-mass spectrometry

A method was established for the determination of genotoxic impurity.in erlotinibhydrochloride(3-ethynylaniline) using liquid chromatography-mass spectrometry. Using the ESI ion source positive ion multireaction monitoring (MRM) mode,the ion pairs 118→75 and 118→91 were selected and measured. The chromatographic column was Thermo Hyperiil GOLD C8(100 mm×4.6 mm,3 μm),the mobile phase was methanol and waterfor gradient elution,the flow rate was 0.4 mL/min,and the column temperature is 35℃.Results showed that the detection mass concentration of 3-ethynylaniline in this method had a good linear relationship in the range of 1.0 to 20 ng/mL, with R²=0.999 4.The relative standard deviation(n=6) of the precision experiment was 1.13%,and the recoveries of standard additions (n=3) at low,medium,and high concentrations were between 90.1% and 106.1%.The method exhibited high sensitivity,specificity,and precision,and it met the requirement for the determination of 3-acetyleniline,a genotoxic impurity in erlotinib hydrochloride tablets.