气相色谱法检测阿普米司特原料药中有机溶剂残留OACSTPCD
Determination of Organic Solvent Residues in Active Pharmaceutical Ingredients of Apremilast by Gas Chromatography
目的 建立测定阿普米司特原料药中 8 种有机溶剂残留量的气相色谱法.方法 色谱柱为DB-624 石英毛细管柱(60m×0.53 mm,3.00µm),程序升温,进样口温度为 220℃,检测器为氢火焰离子化检测器(FID),检测器温度为 250℃,载气为氮气,载气流速为 4 mL/min,分流比为 20∶1,直接进样,进样量为 1µL.结果 甲醇、乙醇、丙酮、乙酸甲酯、乙酸乙酯、乙酸、异丙叉丙酮、二丙酮醇的质量浓度分别在 9.361～593.2µg/mL、10.01～984.6µg/mL、10.23～996.4µg/mL、14.31～971.5µg/mL、10.22～991.4µg/mL、7.313～983.3µg/mL、3.335～201.6µg/mL、10.12～202.4µg/mL范围内与峰面积线性关系良好(r≥0.999 8,n = 4);定量限分别为 9.36,10.01,10.23,14.31,10.22,7.31,3.34,10.12µg/mL,检测限分别为 2.81,3.00,3.07,4.29,3.07,2.19,1.01,3.37µg/mL;精密度、重复性试验结果的RSD均小于 6.0%(n = 6);平均加样回收率分别为 103.25%,103.97%,101.51%,103.58%,102.63%,100.92%,103.67%,103.63%,RSD分别为 2.24%,5.70%,2.15%,1.92%,2.25%,4.54%,3.28%,0.95%(n = 9).3 批样品中乙醇和丙酮的检出量分别为 0.17%,0.16%,0.19%和 0.20%,0.17%,0.21%,其余溶剂均未检出.结论 该方法操作简便、结果准确可靠、灵敏度高,可用于阿普米司特原料药中 8 种有机溶剂残留量的测定.拟订阿普米司特原料药中甲醇、乙醇、丙酮、乙酸甲酯、乙酸乙酯、乙酸、异丙叉丙酮、二丙酮醇的残留限度分别为 0.3%,0.5%,0.5%,0.5%,0.5%,0.5%,0.1%,0.1%.
Objective To establish a gas chromatography method for determination of eight organic solvent residues in active pharmaceutical ingredients(API)of apremilast.Methods The chromatographic column was DB-624 quartz capillary column(60 m×0.53 mm,3.00 µm)with temperature programming,the inlet temperature was 220℃,the detector was flame ionization detector(FID)with temperature of 250℃,the carrier gas was nitrogen with the flow rate of 4 mL/min,the split ratio was 20∶1,and direct injection was adopted with injection volume of 1 µL.Results The linear ranges of methanol,ethanol,acetone,methyl acetate,ethyl acetate,acetic acid,isopropyl deneacetone,and diacetone alcohol were 9.361-593.2 µg/mL,10.01-984.6 µg/mL,10.23-996.4 µg/mL,14.31-971.5 µg/mL,10.22-991.4 µg/mL,7.313-983.3 µg/mL,3.335-201.6 µg/mL,10.12-202.4 µg/mL(r≥0.999 8,n = 4),respectively.The limits of quantification(LOQ)were 9.36,10.01,10.23,14.31,10.22,7.31,3.34,and 10.12 µg/mL,respectively.The limits of detection(LOD)were 2.81,3.00,3.07,4.29,3.07,2.19,1.01,and 3.37 µg/mL,respectively.The RSDs of precision and repeatability test results were less than 6.0%(n = 6).The average recoveries of methanol,ethanol,acetone,methyl acetate,ethyl acetate,acetic acid,isopropyl deneacetone,and diacetone alcohol were 103.25%,103.97%,101.51%,103.58%,102.63%,100.92%,103.67%,and 103.63%with RSDs of 2.24%,5.70%,2.15%,1.92%,2.25%,4.54%,3.28%,and 0.95%(n = 9),respectively.The contents of ethanol in the three batches of samples were 0.17%,0.16%,and 0.19%,respectively.The contents of acetone in the three batches of samples were 0.20%,0.17%,and 0.21%,respectively.No other solvents were detected.Conclusion The method is simple,accurate and reliable with high sensitivity,which can be used for the determination of eight types of organic solvent residues in the API of apremilast.The residual limits for methanol,ethanol,acetone,methyl acetate,ethyl acetate,acetic acid,isopropyl deneacetone,and diacetone alcohol in the API of apremilast are set as 0.3%,0.5%,0.5%,0.5%,0.5%,0.5%,0.1%,and 0.1%,respectively.
杨敏;闫翠勤;徐艳梅;郝丽娟;王春霞
石药集团中奇制药技术<石家庄>有限公司,河北 石家庄 050035河北省药品医疗器械检验研究院,河北 石家庄 050200
药学
阿普米司特气相色谱法有机溶剂乙醇丙酮残留量原料药
apremilastgas chromatographyresidual solventsethanolacetoneresidual volumeactive pharmaceutical ingredients
《中国药业》 2024 (001)
59-63 / 5
河北省自然科学基金[B2022329002].
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