摘要
目的建立测定阿哌沙班原料药中可能残留的12种有机溶剂(甲醇、乙醇、丙酮、异丙醇、叔丁基甲醚、二氯甲烷、醋酸乙酯、四氢呋喃、三乙胺、原甲酸三甲酯、吗啉、N,N-二甲基甲酰胺)的检测方法。方法采用顶空气相色谱法,色谱柱为DB-624毛细管柱(30.0 m×0.53 mm×3.00μm),载气为高纯度氮气;顶空温度为100℃,顶空平衡时间为20 min;柱温40℃,维持6 min,以20℃/min升至220℃,维持10 min;氢火焰离子化检测器(FID),进样口温度为250℃,检测器温度为250℃,体积流量为2.8 m L/min,分流比为5:1。结果在考察的浓度范围内线性关系良好(r=0.999 4~0.999 9),12种残留溶剂均完全分离,精密度试验RSD值以及被测组分的平均回收率均符合要求。结论该气相色谱法操作简单,准确度、灵敏度高,可用于检测阿哌沙班原料药中残留的有机溶剂。
Objective To establish a method for determination of the twelve residual organic solvents, including methanol, ethanol, acetone, isopropanol, ten-Butyl methyl ether, dichloromethane, aceticether, tetrahydrofuran, triethylamine,trimethylorthofor-Mate, morpholine, N,N-Dimethylformamide in Apixaban bulks drug. Methods Gas head-space chromatography was applied to this study. The eolunm was DB-624 silica capillary column （30.0 m × 0.53 mm × 3.00 μm） and the carrier gas was high purity nitrogen; The vial temperature was 100 ℃, and the vial time was 20 min. The Column temperature was kept at 40℃ for 6 min, then the temperature was raised to 220 ℃ at the rate of 20 ℃/min and subsequently sustained for 10 min. FID detector temperature and injection temperature were both 250 ℃. The N2 flow rate was 2.8 mL/min. Split ratio was 5：1. Results Twelve kinds of solvents were completely separated and determined with a good linearity （r = 0.9994-0.9999）.The RSD values of precision experiments and the average recovery was in line with the requirements. Conclusion Theanalytieal method is simple, accurate and sensitive, which could be used for determination of residual organic solvents in Apixaban bulks drug.
出处
《药物评价研究》
CAS
2017年第1期63-67,共5页
Drug Evaluation Research
关键词
阿哌沙班
顶空气相色谱
有机残留溶剂
Apixaban
headspace gas chromatography
residual organic solvents
