顶空气相色谱法同时测定艾司奥美拉唑镁原料药中6种有机溶剂的残留量

Simultaneous Determination of 6 Residual Organic Solvents in Omeprazole Magnesium by Headspace GC

目的:建立同时测定艾司奥美拉唑镁原料药中甲醇、异丙醇、乙腈、二氯甲烷、乙酸乙酯、甲苯6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DB-624毛细管柱,程序升温,进样口温度为200℃,检测器为氢火焰离子化检测器,检测器温度为250℃,载气为氮气,氮气流速为2.0 mL/min,分流比为5∶1,顶空进样量为1 mL,顶空平衡温度为80℃,平衡时间为20 min。结果:甲醇、异丙醇、乙腈、二氯甲烷、乙酸乙酯、甲苯检测质量浓度线性范围分别为12.56~628.00μg/mL(r=0.999 7)、20.22~1 011.20μg/mL(r=0.999 9)、1.96~97.76μg/mL(r=0.999 7)、3.10~154.88μg/mL(r=0.999 8)、20.69~1 034.56μg/mL(r=0.999 8)、3.53~176.72μg/mL(r=0.999 8);定量限分别为1.00、0.91、0.47、0.93、0.41、0.35μg/mL,检测限分别为0.31、0.30、0.14、0.31、0.12、0.11μg/mL;精密度、稳定性、重复性试验的RSD<3%;加样回收率分别为94.53%~101.29%(RSD=2.15%,n=9)、97.78%~103.42%(RSD=1.77%,n=9)、96.99%~105.76%(RSD=2.59%,n=9)、96.83%~102.05%(RSD=1.86%,n=9)、97.98%~101.13%(RSD=0.88%,n=9)、97.80%~102.40%(RSD=1.41%,n=9)。结论:该方法灵敏、准确,可用于艾司奥美拉唑镁原料药中甲醇、异丙醇、乙腈、二氯甲烷、乙酸乙酯、甲苯6种有机溶剂残留量的同时测定。

OBJECTIVE： To establish a method for the simultaneous determination of 6 kinds of residual organic solvents in Omeprazole magnesium, such as methanol, isopropanol, acetonitrile, dichloromethane, ethyl acetate and toluenein. METHODS： Headspace GC was adopted. The determination was performed on the column of DB-624 column by temperature programming. The inlet temperature was 200 ℃, and hydrogen flame ionization detector was adopted with the temperature of 250 ℃ ; nitrogen gas was used as carrier gas with flow rate of 2.0 mL/min; the splitting-radio was 5： 1, and sample size was 1 mL; the headspace tem- perature was 80 ℃ and the equilibrium time was 20 min. RESULTS： The linear range were 12.56-628.00 μg/mL for methanol （r= 0.999 7）, 20.22-1011.20μg/mL for isopropanol （r=0.999 9）, 1.96-97.76 μg/mL for acetonitrile （r=0.999 7）,3.10-154.88 ~tg/mL for dichloromethane （r=0.999 8）, 20.69-1034.56 μg/mL for ethyl acetate （r=0.999 8）, and 3.53-176.72μg/mL for toluene （r= 0.999 8）; the limits of quantitation were 1.00, 0.91, 0.47, 0.93, 0.41 and 0.35μg/mL respectively; the limits of detection were 0.31, 0.30, 0.14, 0.31, 0.12 and 0.11 μg/mL respectively; RSDs of precision, stability and reproducibility tests were lower than 3% ; the recoveries were 94.53%-101.29% （RSD=2.15%, n=9）, 97.78%-103.42% （RSD=l.77%, n=9）, 96.99%-105.76% （RSD=2.59% ,n=9）, 96.83%-102.05% （RSD=1.86% ,n=9）, 97.98%-101.13% （RSD=0.88% ,n=9）and 97.80%-102.40% （RSD----1.41%, n=9）. CONCLUSIONS： The method is sensitive and accurate, can be used for the simultaneous determination of 6 kinds of residual organic solvents in Omeprazole magnesium, such as methanol, isopropanol, acetonitfile, dichloromethane, ethyl acetate and toluenein.