石小娜,侯玲君,赵龙山
SHI Xiaona,HOU Lingjun,ZHAO Longshan

• 1:沈阳药科大学药学院
• 2:瀚盟测试科技(天津)有限公司

摘要(Abstract)：

目的 建立HPLC-MS/MS法测定吲哚布芬中的基因毒性杂质：邻苯二甲醛。方法 采用Agilent Eclipse Plus C_(18)(100 mm×4.6 mm, 3.5μm)色谱柱，水为流动相A,甲醇为流动相B,梯度洗脱，流速为0.55 mL·min~(-1),进样体积为10μL,柱温35℃;采用电子喷雾源ESI,正离子模式采集分析，多反应监测(MRM),离子源温度为550℃。结果 邻苯二甲醛的检测下限为0.102μg·L~(-1);平均加样回收率为96.2%(n=9),加样回收率良好；邻苯二甲醛在0.41～4.07μg·L~(-1)范围内与峰面积呈良好线性关系(r=0.997);对照品溶液和样品加标溶液在8 h内稳定性良好。5批吲哚布芬中均未检测到杂质邻苯二甲醛。结论 所建立的方法简单、准确且专属性好，适用于吲哚布芬中具有基因毒性警示结构的杂质邻苯二甲醛的测定。
Objective To establish an HPLC-MS/MS method for the determination of genotoxic impuritiy phthalaldehyde in indobufe: phthalaldehyde.Methods The separation was performed on an Agilent Eclipse Plus C_(18)(100 mm×4.6 mm, 3.5 μm) column using the mobile phase consisting of Aqueous solution(mobile phase A) and methanol(mobile phase B) by gradient elution at a flow rate of 0.55 mL·min~(-1).The column temperature was 35 ℃ and the injection volume was 10 μL.The electrospray was operated with the source ESI under positive ionization scanning mode was collected and analyzed.The temperature of ion source was 550 ℃.Results The detection limit of phthalaldehyde was 0.102 μg·L~(-1) and the average recovery was 96.2%(n=9).Standard curve of phthalaldehyde was linear within the range of 0.41-4.07 μg·L~(-1)(r=0.997).The control solution and the labeled sample solution were stable after 8 h.No phthalaldehyde was detected in the 5 batches of indobufen.Conclusion The established method is simple, accurate and specific for the determination of genotoxic impuritiy phthalaldehyde in indobufen.

关键词(KeyWords)： 高效液相色谱—串联质谱;吲哚布芬;基因毒性杂质;邻苯二甲醛
HPLC-MS/MS;indobufen;genotoxic impurity;o-phthalaldehyde

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 石小娜,侯玲君,赵龙山
SHI Xiaona,HOU Lingjun,ZHAO Longshan

DOI: 10.14066/j.cnki.cn21-1349/r.2021.0222

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