[关键词]
[摘要]
目的 建立枸橼酸坦度螺酮原料药中间体中潜在基因毒性杂质1,4-二溴丁烷的控制检测方法。方法 采用高效气相色谱(GC)法,使用色谱柱Agilent DB-624(30 m×320 μm,1.8 μm),升温程序:初始柱温95℃,保持2 min,以20℃/min升温至220℃,保持5 min。进样口温度250℃,检测器温度250℃,体积流量3 mL/min;分流比1∶1;进样量1 μL。进行专属性、线性范围、灵敏度、稳定性、重复性、回收率、耐用性方法学考察。结果 1,4-二溴丁烷在0.109 5~1.094 8 μg/mL内峰面积与质量浓度线性关系良好(r=0.998 6);检测限为0.109 5 μg/mL,定量限为0.273 7 μg/mL,平均回收率为116.2%,方法学考察均符合要求。各批次样品中1,4-二溴丁烷的质量分数均小于0.002 5%。结论 建立的方法专属性强、灵敏度高、测定结果准确、操作简单,可用于枸橼酸坦度螺酮原料药中间体中1,4-二溴丁烷的检测。
[Key word]
[Abstract]
Objective To establish a controlled method for the detection of the potential genotoxic impurity 1, 4-dibromobutane in the intermediate of tandospirone citrate API. Methods Agilent DB-624 (30 m×320 μm, 1.8 μm) was used. The initial column temperature was 95℃ for 2 min, and the temperature was 20℃/min to 220℃ for 5 min. The injection port temperature was 250℃, the detector temperature was 250℃, the flow rate was 3 mL/min, the split ratio was 1:1, and the injection volume was 1 μL. Results The linear range of 1, 4-dibromobutane was 0.109 5-1.094 8 μg/mL (r=0.998 6); the limit of detection was 0.1095 μg/mL, the limit of quantification was 0.273 7 μg/mL, the average recovery (n=9) was 116.2%, and the content of 1, 4-dibromobutane in each batch was less than 0.002 5%. Conclusion The method is specific, sensitive, accurate and simple. It can be used for the determination of 1, 4-dibromobutane in the intermediate of tandospirone citrate.
[中图分类号]
R917
[基金项目]