布洛芬原料药中残留有机溶剂和微量金属杂质的检测研究

目的:针对布洛芬的生产工艺,建立原料药中残留有机溶剂(二氯甲烷、乙醇)和微量金属杂质(铝、钴、镍)的检测方法。方法:残留溶剂采用顶空毛细管气相色谱法,使用DB-624毛细管色谱柱(30 m×0.53 mm,膜厚3.0μm),载气为氮气,检测器采用FID,柱温采用程序升温,顶空平衡温度80℃,平衡时间60 min,以N,N-二甲基甲酰胺(DMF)为溶剂;金属杂质采用微波消解-石墨炉原子吸收法测定,通过石墨炉程序升温进行测定。结果:在残留溶剂的测定中,两待测组分之间的分离度为6.3,在测定浓度范围内r分别为0.9999和0.9998,检测限分别为0.2μg.g-1和2μg.g-1,加样回收率分别为101.1%和101.0%。在3种金属杂质的测定中,检测限分别为5 ng.g-1、5 ng.g-1和10 ng.g-1;在测定浓度范围内,r分别为0.9996,0.9993,0.9998;3种待测元素的加样回收率均大于90.0%;结论:测定方法准确可靠,灵敏度高,适用于布洛芬原料药中残留溶剂和微量金属杂质的分析检测。

Study on determination of residual solvents and trace metal impurities in ibuprofen

Objective:Based on the manufacturing process of ibuprofen,to establish an evaluation method for determination of residual solvents(methylene chloride and ethanol) and trace metal impurities(aluminium,cobalt,nickel) contained in API(active pharmaceutical ingredient)of ibuprofen.Methods: DB-624 capillary column(30 m×0.53 mm×3.0 μm) was adopted,the temperature was warmed according to instrument’s procedure,FID was selected as detector.Headspace equilibrium temperature was 80 ℃,equilibrium time was 60 minutes,and N,N-dimethylacetamide was applied as the solvent;microwave digestion-graphite furnace atomic absorption spectrometry was adopted for determine metal impurity through raising temperature by graphite furnace procedure.Results: For residual solvent determination,good linear responses were obtained from the two residual solvents in their respective concentration ranges(r = 0.9998,0.9999),furthermore,the limits of detection were 0.2 and 2 μg·g-1,respectively.The average recoveries of three concentration levels were 101.0% and 101.1%,respectively.For metal impurity determination,the limits of detection were 5 ng·g-1,5 ng·g-1 and 10 ng·g-1,respectively,and r = 0.9996,0.9993 and 0.9998 in their respective concentration ranges.The recoveries of three metal elements based on three concentrations were all above 90.0%.Conclusions: The developed method is simple,sensitive,and accurate for the residual solvents and trace metal impurities analysis of ibuprofen API.