建立同时测定利奥西呱原料药中残留溶剂甲醇、异丙醇、二氯甲烷、正己烷、乙酸乙酯、六甲基二硅醚、三乙胺、甲苯与N,N-二甲基甲酰胺残留量的方法.采用顶空进样气相色谱法,以二甲基亚砜为溶剂,外标法计算残留溶剂量.9种残留溶剂色谱峰的理论板数均>10000,相邻峰的分离度均>1.5,在考察的浓度范围内各溶剂线性关系良好(r=0.9982~0.9997);RSD<10%;平均加标回收率为90.86﹪~105.01﹪o各残留溶剂的检测限和定量限分别为0.000025%~0.0026%,0.000051%~0.0088%,均低于《中国药典》规定.利奥西呱原料中检出甲醇、正己烷、乙酸乙酯与DMF残留,但均未超过限度,其余溶剂未检出.该方法操作简单、方法灵敏、结果准确,可用于利奥西呱原料药中残留溶剂检测.%To establish a method for simultaneous determination of the nine residual solvents (methanol, isopropanol, dichloromethane, normal hexane, ethyl acetate, hexamethyl disiloxane, triethylamine, methylbenzene and N,N-dimethylformamide) in Riociguat. Headspace gas chromatography was applied and dimethyl sulfoxide solvent was used. External standard method was adopted to calculate residual solvent content. The good linear relation of 9 kind of organic solvents were achieved (r=0.9982~0.9997) with theoretical plate number at chromatographic peak being >10000 and resolution of adjacent peak being >1.5 within investigated concentration range. The RSDs of precision was <10%. The average recoveries ranged from 90.86% to 105.01%. Detection limit and quantitation limit (percentage in sample for test) were 0.000025%~0.0026%,0.000051%~0.0088%, which is lower than the regulations in Chinese Pharmacopoeia. The methanol, normal hexane, ethyl acetate and DMF were detected in Riociguat, and they are within limit. No other solvents detected. The analytical method is simple, accurate and sensitive, and is suitable for the determination of residual solvents in Riociguat.
展开▼
