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×320μm,1.8μm),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1μL。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0.1095~1.0948μg/mL内峰面积与质量浓度线性关系良好(r=0.9986);检测限为0.1095μg/mL,定量限为0.2737μg/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0.0025%。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。
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×320μm,1.8μm)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 was250℃,the detector temperature was 250℃,the flow rate was 3 mL/min,the split ratio was 1:1,and the injection volume was 1μL.Results The linear range of 1,4-dibromobutane was 0.1095—1.0948μg/mL(r=0.9986);the limit of detection was 0.1095μg/mL,the limit of quantification was 0.2737μg/mL,the average recovery(n=9)was 116.2%,and the content of 1,4-dibromobutane in each batch was less than 0.0025%.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.
作者
徐意华
山广志
代相成
XU Yihua;SHAN Guangzhi;DAI Xiangcheng(Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences,Beijing 100050,China;Zhi zhuo medical technology(Beijing)Co.,Ltd,Beijing 101102,China)
出处
《药物评价研究》
CAS
2021年第9期1923-1926,共4页
Drug Evaluation Research
