气相色谱法测定利格列汀中基因毒杂质氯乙腈

Determination of Chloroacetonitrile in Linagliptin by Gas Chromatography

建立了气相色谱法检测利格列汀中的基因毒杂质氯乙腈。采用DB-FFAP型毛细管柱(30 m×0.53 mm×0.5μm),固定液为硝基对苯二甲酸改性的聚乙二醇;程序升温,起始温度为50℃,维持2 min,以10℃/min的速率升温至180℃,维持5 min;进样口温度为160℃;检测器温度为200℃;载气为氮气;流速为1.5 ml/min;分流比为10∶1;进样量为1μl。结果显示,氯乙腈在17.42~69.70 ng/ml内,线性关系良好(r=0.9996),定量限和检测限浓度分别为17.42、6.1μg/ml。低、中、高浓度样品的平均加样回收率(n=9)分别为95.5%、100.4%、108.6%,RSD分别为7.66%、9.14%、5.03%。经方法学验证,建立的方法可用于利格列汀中基因毒杂质氯乙腈的检测,为其质量控制提供了参考。

A gas chromatography method was established to detect the genotoxic impurity chloroacetonitrile in linagliptin.The DB-FFAP column(30 m×0.53 mm×0.5μm)was used,and the fixed liquid was polyethylene glycol that modified by nitroterephthalic acid.The initial column temperature at 50℃was maintained for two minutes,then the temperature was increased to 180℃at a rate of 10℃/min,and the final temperature was kept for five minutes.The temperature of the injection port was 160℃,the temperature of the detector was 200℃,the flow rate of nitrogen was 1.5 ml/min,the split ratio was 10∶1 and the injection volume was 1μl.The results showed that it was linear for chloroacetonitrile in the range of 17.42-69.70 ng/ml(r=0.9996).The limits of quantification and detection were 17.42 and 6.1μg/ml,respectively.The average recoveries of low,medium and high concentrations(n=9)were 95.5%,100.4%and 108.6%respectively,with the RSDs of 7.66%,9.14%and 5.03%.After methodological verification,the established method could be used to detect the genotoxic impurity chloroacetonitrile in linagliptin,which provided a reference for its quality control.