毛细管气相色谱法测定非洛地平原料药有机溶剂残留.docVIP

毛细管气相色谱法测定非洛地平原料药有机溶剂残留 李晶*，陈玉华，王东武 ，于忠文，李宗文，高永吉 （迪沙药业集团有限公司，威海 264200） 摘要：【目的】 建立了毛细管气相色谱法检测非洛地平原料药中乙醇、丙酮、异丙醇、二氯甲烷、乙酸乙酯、吡啶残留溶剂的分析方法。【方法】采用手动进样程序升温法，FID检测器，6%-氰丙基苯基-94%-二甲基聚硅氧烷为固定液Determination of Residual Organic Solvents in Felodipine by Capillary Gas Chromatography Li Jing, Chen Yuhua, Wang Dongwu, Yu Zhongwen, Li Zongwen, Gao Yongji (Disha pharmaceutical Group,Weihai 264200,China ) Abstract：0bjecive To develop the capillary gas chromatography method for the determination of residual organic solvents ethanol，acetone, dichloromethane,ethyl acetate and pyridine in felodipine．Methods The samples were injected by sampling with program heating and FID detector .The determination was performed on DB-624 capillary column（30m×0.32mm,0.25μm）with 6% - cyanide phenyl - 94% - two methyl polysiloxane copolymer which stationary liquid is. Results Linear response were obtained for ethanol，acetone, dichloromethane,ethyl acetate and pyridine in their respective concentration ranges (r=0.9803～0.99,n=5),and the limits of detection were0.16～1.6ng, the limits of quantity were 3.1～g.The average recoveries of three concentration levels were 99.49～103.00%，with RSD 1.8～6.4%(n=5)。Conclusions the developed method is simple,sensitive and accurate with good reproducibility.It can be used for the residual solvent analysis in glimepiride samples. Key words: manual sampling; gas chromatography; felodipine; residual solvent药品中的残留溶剂是指在原料药或辅料的生产中，以及制剂制备过程中使用的，但在工艺过程中未能完全去除的有机溶剂[1]。非洛地平是选择性钙离子拮抗类降压药，本公司在生产非洛地平原料药过程中引入种有机溶剂，根据有关残留溶剂的规定，氯甲烷、吡啶属于二类溶剂，限度依次为0.06%、0.02%；乙醇、丙酮、异丙醇、乙酸乙酯属于三类溶剂，限度0.5%[2]。由于填充柱较多的溶剂得到好的分离毛细管柱因柱效高，可以同时分离多种物质而被广泛应用于残留物质的检测。Varian气相色谱仪，FID检测器，色谱柱：DB-624（6%氰丙基苯基-94%二甲基硅氧烷为固定液）毛细管色谱柱（30m×0.53mm×μm）；非洛地平原料药(迪沙药业集团药物研究院有机合成研究所，批号为DSH015-02-020-000173，DSH015-02-020-000173，DSH015-02-020-000173溶剂为N、N-二甲基甲酰胺（DMF），乙醇、丙酮、异丙醇、二氯甲烷、乙酸乙酯、吡啶均为分析纯固定液6%氰丙基苯基-94%二甲基硅氧烷为 图1 溶剂DMF色谱图 Figure 1 GC chromatogram of DMF 图2 混合对照品溶液色谱图 Figure2 GC chromatogram of mixed reference solution 1 乙醇(etho