顶空气相色谱法测定利伐沙班原料药中甲胺的残留量

Determination of Residual Methylamine in Rivaroxaban by Headspace Gas Chromatography

目的:建立顶空气相色谱法测定利伐沙班原料药中甲胺的含量。方法:采用顶空气相色谱法,色谱柱为Agilent CP-Volamine(30 m×0.32 mm)毛细管柱;经程序升温,起始温度为35℃,维持8 min,以每分钟25℃的速率升温至200℃,维持6 min;载气为氮气,流速为1.5 mL/min;氢火焰离子化检测器(FID),检测器温度220℃;顶空进样,顶空瓶平衡温度为90℃,平衡时间为30 min;进样口温度200℃;分流比为20∶1。结果:在本文的色谱条件下,甲胺与样品中其他潜在残留溶剂均能得到有效分离,其定量限为0.8μg/mL,其质量浓度在2.50~62.45μg/mL(r=0.9996)范围内线性关系良好,平均回收率(n=9)为97.5%,RSD为6.5%。结论:该方法操作简便,专属,灵敏,准确性高,可作为利伐沙班原料药中甲胺的测定方法。

Objective:To establish a headspace gas chromatography method for the determination of residual Methylamine in rivaroxaban.Methods:Headspace gas chromatography was adopted with Agilent CP-Volamine capillary column(30 m×0.31 mm)and the temperature was programmed at 35℃maintained for 8 min,at a rate of 25℃/min to 200℃maintained for 6 min,and the carrier gas was nitrogen and the column flow rate was 1.5 mL/min.The temperature of flame ionization detector was set at 220℃.Headspace injection was applied with the balance temperature of headspace bottle at 90℃,the balance time was 30 min,and the inlet temperature was 200℃,and the injection split ratio was 20∶1.Results:Methylamine and other residual organic solvents in rivaroxaban were completely separated by the method.The limit of quantification was 0.8μg/mL.Good linearity of Methylamine was obtained within the range of 2.50~62.45μg/mL(r=0.9996).The average recovery was 97.5%and the RSD was 6.5%.Conclusion:The established method is simple,sensitive and accurate and can be used for the determination of residual methylamine in rivaroxaban.