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

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

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。

Objective：Based on the manufacturing process of ibuprofen, to establish an evaluation method for de- termination 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 spec- trometry 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^-1respectively, 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.