气相色谱法测定凡德他尼原料药中8种有机溶剂残留量
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摘要
目的:建立同时测定凡德他尼原料药中8种有机溶剂即甲醇、乙醇、四氢呋喃、正己烷、二氯甲烷、乙酸乙酯、异丙醇、N,N-二甲基甲酰胺含量的方法。方法:采用毛细管气相色谱法,以二甲基亚砜(DMSO)为溶剂,按外标法计算溶剂残留量。色谱柱为DB-624,进样口温度为250℃,氢火焰离子化检测器温度为270℃,程序升温,载气为N2,分流比为20∶1。结果:8种有机溶剂在各自的检测质量浓度范围内线性关系良好(r=0.998 1~0.999 4);平均加样回收率为95.90%~101.4%(RSD=0.56%~3.16%,n=3);3批样品中有1批检出四氢呋喃和N,N-二甲基甲酰胺。结论:建立的方法操作简单、灵敏、结果准确,可用于凡德他尼原料药中有机溶剂残留量检查。
OBJECTIVE:To develop a method for the content determination of 8 residual organic solvents as methanol,ethanol,tetrahydrofuran,n-hexane,dichlormethane,ethyl acetate,isopropanol,N,N-dimethylformamide in vandetanib raw material.METHODS:Gas chromatography method was adopted using DMSO as solvent. The contents of residual solvent were determined by external standard method. The determination was performed on DB-624 column with FID detector. The injector temperature was set at 250 ℃ and the detector temperature was 270 ℃ by temperature programming. Carrier gas was nitrogen,and the splitting ratio was 20 ∶ 1. RESULTS:The good linear relation of 8 kind of organic solvents were achieved(r=0.998 1-0.999 4). The average recoveries were ranged from 95.90% to 101.4%(RSD=0.56%-3.16%,n=3). Among 3 batches of samples,tetramethylene oxide and N,N-dimethylfomamide were detected in 1 batch of sample. CONCLUSIONS:The method is simple,sensitive and accurate,and can be used for the determination of residual organic solvents in vandetanib raw material.
OBJECTIVE:To develop a method for the content determination of 8 residual organic solvents as methanol,ethanol,tetrahydrofuran,n-hexane,dichlormethane,ethyl acetate,isopropanol,N,N-dimethylformamide in vandetanib raw material.METHODS:Gas chromatography method was adopted using DMSO as solvent. The contents of residual solvent were determined by external standard method. The determination was performed on DB-624 column with FID detector. The injector temperature was set at 250 ℃ and the detector temperature was 270 ℃ by temperature programming. Carrier gas was nitrogen,and the splitting ratio was 20 ∶ 1. RESULTS:The good linear relation of 8 kind of organic solvents were achieved(r=0.998 1-0.999 4). The average recoveries were ranged from 95.90% to 101.4%(RSD=0.56%-3.16%,n=3). Among 3 batches of samples,tetramethylene oxide and N,N-dimethylfomamide were detected in 1 batch of sample. CONCLUSIONS:The method is simple,sensitive and accurate,and can be used for the determination of residual organic solvents in vandetanib raw material.
引文
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[2]沈永洲,沈高飞,祝丽娟.海宁市1977-2010年甲状腺癌发病趋势分析[J].中国慢性病预防与控制,2012,20(2):203.
[3]陈和新,王娜,黄培新,等.2002-2008年江苏省海门市甲状腺癌流行状况分析[J].中华疾病控制杂志,2011,15(4):279.
[4]敖小凤,高志红.甲状腺癌流行现状研究进展[J].中国慢性病预防与控制,2008,16(2):217.
[5]夏训明.美国FDA批准首种治疗甲状腺髓样癌新药Vandetanib[J].广东药学院学报,2011,27(2):173.
[6]赵兴旺,赵临襄.凡德他尼:Vandetanib[J].中国药物化学杂志,2011,21(5):405.
[7]ASTRAZENECA PLC.FDA approves orphan drug vandetanib[EB/OL].(2011-04-07)[2013-07-01].http://www.astrazeneca.com/Media/Press-releases/Article/20100407-fda-approves-orphan-drug-vandetanib.
[8]祝业,龙旭梅,张建平,等.治疗甲状腺髓样癌新药凡德他尼[J].中国新药杂志,2012,21(17):159.
[9]丁香园医药数据库.凡德他尼[DB/OL].(2006-04-27)[2013-07-01].http://db.dxy.cn/drugSearch/.
[10]国家药典委员会.中华人民共和国药典:二部[S].2010年版.北京:中国医药科技出版社,2010:686、附录61-65.
[11]陈立亚,于宝珠,赵慧芳.ICH指导原则与各国现行药典药品的残留溶剂分析方法概述[J].中国药事,2005,19(9):542.