摘要
目的建立同时测定国产米格列奈钙原料药中甲醇、乙醇、异丙醇、乙腈、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、三乙胺等有机溶剂残留量的顶空气相色谱法。方法色谱柱为DB-624毛细管色谱柱(以6%氰丙基苯基-94%二甲基聚硅氧烷为固定液,60 m×0.53 mm,3μm),程序升温,进样口温度为220℃,检测器为火焰离子化检测器(FID),温度为250℃,载气为氮气,载气流速为2.0 m L/min,分流比为10∶1,顶空加热温度为80℃,平衡时间为30 min。结果甲醇、乙醇、异丙醇、乙腈、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、三乙胺的质量浓度分别在0.03~0.45 mg/m L,0.05~0.75 mg/m L,0.05~0.75 mg/m L,0.0041~0.0610 mg/m L,0.006~0.089 mg/m L,0.003~0.045 mg/m L,0.05~0.75 mg/m L,0.0073~0.1100 mg/m L,0.002~0.030 mg/m L范围内与峰面积线性关系良好(r均大于0.995);检测限分别为1.50,2.50,1.00,0.41,0.59,0.06,0.50,0.37,0.40μg/m L,定量限分别为3.00,5.00,2.50,2.00,1.20,0.15,1.00,1.50,0.99μg/m L;精密度试验的RSD分别为5.07%,5.46%,5.16%,5.14%,3.91%,4.77%,3.71%,3.75%,4.62%(n=6);平均加样回收率分别为98.73%,98.85%,99.46%,100.91%,95.67%,106.85%,102.35%,100.79%,102.53%,RSD分别为3.17%,3.31%,3.27%,3.34%,2.97%,3.40%,2.78%,2.85%,3.72%(n=6)。国内5个厂家的15批次米格列奈钙原料药样品中均未检出上述9种有机溶剂残留。结论所建立的方法可用于国产米格列奈钙原料药中有机溶剂残留的测定;国产米格列奈钙原料药中有机溶剂残留控制情况较好。
Objective To establish a headspace chromatographic method for the simultaneous determination of nine kinds of organic solvent residues(methanol,ethanol,isopropanol,acetonitrile,dichloromethane,n-hexane,ethyl acetate,tetrahydrofuran,and triethylamine)in the domestic active pharmaceutical ingredients(API)of mitiglinide calcium.Methods The chromatographic column was DB-624 capillary column(6%cyanopropyl phenyl-94%dimethylpolysiloxane was taken as the stationary phase,60 m×0.53 mm,3μm)with temperature-programmed,the temperature of the injection port was 220℃,the detector was flame ionization detector(FID)with temperature of 250℃,the carrier gas was nitrogen with flow rate of 2.0 m L/min,the split ratio was 10∶1,the headspace heating temperature was 80℃,and the equilibrium time was 30 min.Results The linear ranges of methanol,ethanol,isopropanol,acetonitrile,dichloromethane,n-hexane,ethyl acetate,tetrahydrofuran and triethylamine were 0.03-0.45 mg/mL,0.05-0.75 mg/mL,0.05-0.75 mg/mL,0.0041-0.0610 mg/m L,0.006-0.089 mg/m L,0.003-0.045 mg/m L,0.05-0.75 mg/m L,0.0073-0.1100 mg/m L,0.002-0.030 mg/m L(r>0.995),their limits of detection(LOD)were 1.50,2.50,1.00,0.41,0.59,0.06,0.50,0.37 and 0.40μg/m L,respectively,and their limits of quantitation(LOQ)were 3.00,5.00,2.50,2.00,1.20,0.15,1.00,1.50 and 0.99μg/m L,respectively.The RSDs of their precision tests were 5.07%,5.46%,5.16%,5.14%,3.91%,4.71%,3.71%,3.75%and 4.62%(n=6),respectively.The average recoveries of methanol,ethanol,isopropanol,acetonitrile,dichloromethane,n-hexane,ethyl acetate,tetrahydrofuran and triethylamine were 98.73%,98.85%,99.46%,100.91%,95.67%,106.85%,102.35%,100.79%,102.53%with RSDs of 3.17%,3.31%,3.27%,3.34%,2.97%,3.40%,2.78%,2.85%and 3.72%(n=6),respectively.The above nine organic solvent residues were not detected in 15 batches of API of mitiglinide calcium from five domestic manufacturers.Conclusion The established method can be used for the simultaneous determination of organic solvent residues in the domestic API of mitiglinide calcium.The
作者
李珉
侯金凤
刘海涛
车宝泉
李文东
LI Min;HOU Jinfeng;LIU Haitao;CHE Baoquan;LI Wendong(Beijing Institute of Drug Control·NMPA Key Laboratory for Research and Evaluation of Generic Drugs·Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing,China 102206)
出处
《中国药业》
CAS
2021年第17期61-64,共4页
China Pharmaceuticals
关键词
米格列奈钙
原料药
有机溶剂残留
顶空气相色谱法
mitiglinide calcium
active pharmaceutical ingredients
organic solvent residues
headspace gas chromatography
