顶空毛细管气相色谱法测定倍他米松磷酸钠原料药中3种有机溶剂残留量

Determination of 3 Kinds of Residual Organic Solvents in Betamethasone Sodium Phosphate Raw Material by Headspace Capillary Gas Chromatography

目的:建立以顶空进样毛细管气相色谱内标法测定倍他米松磷酸钠原料药中3种有机溶剂(四氢呋喃、甲醇、乙醇)残留量的方法。方法:以水为溶剂,正丙醇为内标,色谱柱为HP-INNOWAX(聚乙二醇)毛细管柱,柱温为60℃,进样口温度为180℃,氢火焰离子化检测器检测口温度为250℃,氮气流速为1.0mL·min-1,分流进样,分流比为10∶1,顶空温度为80℃,平衡时间为30min,进样时间为1min。结果:被测溶剂与内标均能得到良好分离,四氢呋喃、甲醇、乙醇检测浓度线性范围分别为0.0144～0.0718、0.060～0.300、0.0993～0.497mg·mL-1(r=0.9993～1.0000);回收率分别为103.7%、95.8%、95.0%,RSD分别为0.53%、0.30%、0.48%(n=6);最低定量浓度分别为0.0573、0.486、0.145μg·mL-1;3批样品中溶剂残留量均符合《中国药典》规定。结论:该方法简单、灵敏、准确,可用于倍他米松磷酸钠原料药中的有机溶剂残留量的检测。

OBJECTIVE： To establish headspace capillary gas chromatography for the content determination of 3 kinds of residual organic solvent （furanidine,methanol and ethanol） in betamethasone sodium phosphate raw material.METHODS： The sample was dissolved in water and n-propanol was used as internal standard.The residual solvent in betamethasone sodium phosphate was separated on HP-INNOWAX （PEG） capillary column with column temperature set at 60 ℃.The injector temperature and FID detector temperature were controlled at 180 ℃ and 250 ℃,respectively.The carried gas was nitrogen at flow rate of 1.0 mL·min-1.The splitting-ratio was 10 ∶ 1.The containers of head-space injector were in equilibrium at 80 ℃ for 30 min.Injection time was 1 min.RESULTS： With this chromatographic condition,those solvents could be separated completely.The linear range were 0.014 4～0.071 8 mg·mL-1 for furanidine,0.060～0.300 mg·mL-1 for methanol and 0.099 3～0.497 mg·mL-1 for ethanol.The average recovery were 103.7% （RSD=0.53%,n=6）,95.8% （RSD=0.30%,n=6） and 95.0% （RSD=0.48%,n=6） respectively.The minimum quantitation limit were 0.057 3 μg·mL-1,0.486 μg·mL-1,0.145 μg·mL-1,respectively.3 kinds of residual organic solvents were all in line with the standard stated in Chinese Pharmacopeia.CONCLUSION： The established method is simple,sensitive and accurate for the content determination of residual solvents in betamethasone sodium phosphate raw material.