顶空气相色谱法同时测定硫酸阿扎那韦原料药中8种有机溶剂残留量

Simultaneous Determination of 8 Residual Solvents in Atazanavir Sulfate Raw Material by Headspace GC

目的:建立同时测定硫酸阿扎那韦原料药中8种有机溶剂残留量的方法。方法:采用顶空气相色谱法,色谱柱为DM-624毛细管柱,程序升温:起始温度40℃,维持22 min,以100℃·min-1的速率升温至120℃,维持10 min;进样口温度为200℃,氢火焰离子化(FID)检测器;检测器温度为250℃;载气为高纯氮气,分流比为10∶1;柱流速为3.0 ml·min-1,顶空平衡温度为70℃,平衡时间为30 min,顶空进样体积为1 ml。结果:异丙醇、正庚烷、甲基叔丁基醚、四氢呋喃、二氯甲烷、甲醇、异丙醚和丙酮检测质量浓度线性范围分别为1.00~700.00μg·ml-1(r=0.9979)、0.167~700.00μg·ml-1(r=0.9967)、0.20~700.00μg·ml-1(r=0.9983)、0.72~100.80μg·ml-1(r=0.9990)、1.20~84.00μg·ml-1(r=0.9988)、0.378~420.00μg·ml-1(r=0.9982)、0.167~14.00μg·ml-1(r=0.9982)、0.20~700.00μg·ml-1(r=0.9987);平均回收率分别为98.26%(RSD=2.67%),100.1%(RSD=2.08%),102.6%(RSD=1.88%),100.1%(RSD=0.55%),99.67%(RSD=1.08%),98.58%(RSD=1.17%),104.1%(RSD=1.93%),100.7%(RSD=0.53%)(n=9)。结论:该方法操作简单、准确、专属性强、耐用性好,可用于硫酸阿扎那韦原料药中8种有机溶剂残留的同时测定。

Objective:To establish a method for the simultaneous determination of 8 residual solvents in atazanavir sulfate raw material.Methods:The headspace gas chromatography was performed on a DM-624 capillary column with programmed temperature:the initial temperature was 40℃,maintained for 22 min,raised to 120℃at a rate of 100℃·min-1,and maintained for 10 min.The injector port temperature was 200℃and the FID detector temperature was at 250℃.Using nitrogen with high purity as the carrier gas,the flow rate was 3.0 ml·min-1.The split ratio was 10∶1.The headspace equilibrium temperature was 70℃,headspace equilibrium time was 30 min,and the sample size was 1 ml.Results:The linear range of isopropanol,n-heptane,methyl tertiary butyl ether,tetrahydrofuran,dichloromethane,methanol,isopropyl ether and acetone was 1.00-700.00μg·ml-1(r=0.9979),0.167-700.00μg·ml-1(r=0.9967),0.20-700.00μg·ml-1(r=0.9983),0.72-100.80μg·ml-1(r=0.9990),1.20-84.00μg·ml-1(r=0.9988),0.378-420.00μg·ml-1(r=0.9982)0.167-700.00μg·ml-1(r=0.9982)and 0.20-700.00μg·ml-1(r=0.9987),respectively.The average recovery was 98.26%(RSD=2.67%),100.1%(RSD=2.08%),102.6%(RSD=1.88%),100.1%(RSD=0.55%),99.67%(RSD=1.08%),98.58%(RSD=1.17%),104.1%(RSD=1.93%)and 100.7%(RSD=0.53%)(n=9),respectively.Conclusion:The method is simple,accurate,reproducible and durable,and can be used for the simultaneous determination of 8 residual solvents in atazanavir sulfate raw material.