LC-MS测定甲磺酸伊马替尼中基因毒性杂质的含量

目的: 建立LC-MS法测定甲磺酸伊马替尼中基因毒性杂质的含量。 方法: 采用Inertsil ODS-3 C₁₈色谱柱(250 mm×4.6 mm,5 μm);流动相A为10 mmol·L^-1甲酸铵溶液(用甲酸调pH至3.2),流动相B为甲醇,梯度洗脱(0~10 min,45%B;10~17 min,45%→80%B;17~22 min,80%B;22~23 min,80%→45%B;23~33 min,45%B);流速为1.0 mL·min^-1;柱温为35℃;采用正离子模式采集数据。 结果: 杂质507-00进样是在0.018~0.734 ng范围内,与峰面积呈良好线性关系,线性方程为Y=8.909×10⁴X-453.2, r=0.9999;检测限0.007 ng;定量限为0.018 ng;平均回收率为90.9%,RSD为3.6%(n=9)。 结论: 本方法简便准确,可用于甲磺酸伊马替尼中基因毒性杂质的检测。

Objective: To establish an LC-MS analytical method for the determination of genotoxic impurities in imatinib mesylate. Method: The method was achieved on an Inertisl ODS-3 C₁₈ column(250 mm×4.6 mm,5 μm)utilizing a mobile phase of 10 mmol·L^-1 ammonium formate(pH adjusted to 3.2 with formic acid)(A)-methanol(B)with gradient elution(0-10 min,45%B;10-17 min,45%→80%B;17-22 min,80%B;22-23 min,80%→45%B;23-33 min,45%B)at the flow rate of 1.0 mL·min^-1.The temperature of column was set at 35℃;The data was acquired in positive ion mode. Results: Standard curve was linear in the range of 0.018-0.734 ng(r=0.9999);The values of limit of quantification and limit of detection were 0.007 ng and 0.018 ng,respectively.The recovery(n=9)of impurity 507-00 was 90.9% and RSD was 3.6%. Conclusion: The method is convenient and sensitive for the determination of genotoxic impurities in imatinib mesylate.

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