吲哚布芬中基因毒性杂质邻苯二甲醛液质联用分析方法的建立  

Determination of genotoxic impurity phthalaldehyde in indobufen by high performance liquid chromatography-tandem mass spectrum

作　　者：石小娜 侯玲君 赵龙山[1] SHI Xiaona;HOU Lingjun;ZHAO Longshan(Shool of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Harmonia Testing(Tianjin)Co.,Ltd.,Tianjin 300457,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]瀚盟测试科技(天津)有限公司,天津300457

出　　处：《沈阳药科大学学报》2023年第3期281-286,共6页Journal of Shenyang Pharmaceutical University

摘　　要：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,3.5μm)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 10μL.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 0.102μg·L^(-1)and the average recovery was 96.2%(n=9).Standard curve of phthalaldehyde was linear within the range of 0.41-4.07μg·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：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 

分 类 号：R917[医药卫生—药物分析学]