顶空气相色谱法测定雷贝拉唑钠原料药中残留溶剂含量
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摘要
利用气相色谱法测定雷贝拉唑钠原料药中丙酮、乙腈、二氯甲烷、乙酸乙酯和甲苯5种有机溶剂残留量,通过优化实验条件建立了一种有效的测定有机溶剂残留量的方法。采用顶空毛细管气相色谱法,检测器为氢火焰离子化检测器,色谱柱为DB-624石英毛细管柱,以氮气为载气,流速为2.0mL/min;柱温采取程序升温方式,于40℃保持8min,然后以每分钟20℃的速率升温至240℃,并保持20min;顶空平衡温度为90℃,平衡时间为30min;进样口温度为200℃,检测温度为250℃;进样体积为1mL,分流比为5∶1。5种有机溶剂在该色谱条件下均能有效分离,峰面积与浓度呈现良好的线性关系,相关系数R圴大于0.990,检出限(3S/N)分别为0.616,6.72,4.89,2.70,1.46μg/mL,定量限(10S/N)分别为1.85,16.8,13.9,8.07,3.64μg/mL,各残留溶剂的加标回收率均在90%~110%范围内。
A gas chromatography(GC)method was developed for the determination of five residual solvents including acetone,acetonitrile,dichloromethane,ethyl acetate and toluene in rabeprazole sodium raw material.Based on the optimized experimental conditions,an effective method for determining the residual amount of organic solvent was established.A headspace capillary GC with FID detector was selected to determine 5kinds of organic as acetone,acetonitrile,dichloromethane,ethyl acetate and toluene.The determination was performed on DB-624 capillary column with nitrogen gas as carrier gas at the rate of 2.0 mL/min.The column temperature was controlled by aprogram of initial column temperature of40 ℃,maintaining for 8min,then raising to 240 ℃ at a rate of 20 ℃ /min,maintaining for20 min.The headspace equilibrium temperature was 90℃and equilibrium time was 30 min.The temperature of the injector was maintaining at 200 ℃ and that of detector at 250 ℃.The injection volume of sample was 1mL,and the split ratio was 5:1.The five residual sol-vents were separated completely under given chromatogram systems.The calibration curve of each solvent showed a good linear relationship,and the correlation coefficients(R)of each solvent is more than 0.990.The limits of detection(3S/N)were 0.616,6.72,4.89,2.70,1.46μg/mL,and the limits of quantitation(10S/N)were 1.85,16.8,13.9,8.07,3.64μg/mL,respectively.The recoveries of each solvent from standard addition were all in the range of 90%~110%.
A gas chromatography(GC)method was developed for the determination of five residual solvents including acetone,acetonitrile,dichloromethane,ethyl acetate and toluene in rabeprazole sodium raw material.Based on the optimized experimental conditions,an effective method for determining the residual amount of organic solvent was established.A headspace capillary GC with FID detector was selected to determine 5kinds of organic as acetone,acetonitrile,dichloromethane,ethyl acetate and toluene.The determination was performed on DB-624 capillary column with nitrogen gas as carrier gas at the rate of 2.0 mL/min.The column temperature was controlled by aprogram of initial column temperature of40 ℃,maintaining for 8min,then raising to 240 ℃ at a rate of 20 ℃ /min,maintaining for20 min.The headspace equilibrium temperature was 90℃and equilibrium time was 30 min.The temperature of the injector was maintaining at 200 ℃ and that of detector at 250 ℃.The injection volume of sample was 1mL,and the split ratio was 5:1.The five residual sol-vents were separated completely under given chromatogram systems.The calibration curve of each solvent showed a good linear relationship,and the correlation coefficients(R)of each solvent is more than 0.990.The limits of detection(3S/N)were 0.616,6.72,4.89,2.70,1.46μg/mL,and the limits of quantitation(10S/N)were 1.85,16.8,13.9,8.07,3.64μg/mL,respectively.The recoveries of each solvent from standard addition were all in the range of 90%~110%.
引文
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[11]陈文丽,杨鹏,俞利林,等.顶空毛细管气相色谱法测定奥拉西坦中乙醇、二氯甲烷和4-氯乙酰乙酸乙酯的残留量[J].中南药学,2015,13(1):74-76.CHEN Wen-li,YANG Peng,YU Li-lin,et al.HS-GC determination of residues of ethanol,dichloromethane and ethyl 4-chloraacetoacetate in oxiracetam[J].Central South Pharmacy,2015,13(1):74-76.
[12]国家药典委员会.中华人民共和国药典:2015版4部[K].北京:中国医药科技出版社,2015:105-109.National Pharmacopoeia Committee.China Pharmacopoeia:4edition 2015[K].Beijing:China Medical Science Press,2015:105-109.
[2]吉丹丹,张玲,谭淑珍,等.高效液相色谱法测定右旋雷贝拉唑钠的对映体纯度[J].理化检验,2015,51(7):1010-1013.JI Dan-dan,ZHANG Ling,TAN Shu-zhen,et al.Determination of enantiomeric purity of rabeprazole sodium by HPLC[J].Physical Testing and Chemical,2015,51(7):1010-1013.
[3]Reddy P R,Himabindu V,Jaydeepkumar L,et al.An improved process for the production of rabeprazole sodium substantially free from the impurities[J].Organic Process Research and Development,2009(13):896-899.
[4]Waser M,Obermuller R,Wiegand J M,et al.Development of a scalable and safe process for the production of 4-Chloro-2,3-dimethylpyridine-N-oxide as a key intermediate in the synthesis of proton pump inhibitors[J].Organic Process Research and Development,2010(14):562-567.
[5]陈敖,王智慧.雷贝拉唑钠的合成[J].精细与专用化学品,2010,18(2):28-29.CHEN Ao,WANG Zhi-hui.Synthesis of rabeprazole[J].Fine and Specialty Chemicals,2010,18(2):28-29.
[6]邱飞,刁勇.雷贝拉唑钠的合成[J].中国医药工业杂志,2010,41(1):9-10.QIU Fei,DIAO Yong.Synthesis of rabeprazole[J].Chinese Journal of Phannaceuticals,2010,41(1):9-10.
[7]王佩,唐金龙.雷贝拉唑钠中残留溶剂的测定[J].中国医药科学,2013,3(2):106-107.WANG Pei,TANG Jin-long.Determination of residual solvents in rabeprazole[J].China Medical Science,2013,3(2):106-107.
[8]张悦杨,程智.GC测定枸橼酸坦度螺酮中的残留溶剂[J].中国现代应用药学,2015,32(6):721-724.ZHANG Yue-yang,CHENG Zhi.Determination of residual organic solvents in tandospirone citrate by GC[J].Chinese Journal of Modern Applied Pharmacy,2015,32(6):721-724.
[9]张素娟,张旭,杨丽霞,等.甲苯磺酸索拉非尼中残留溶剂的离子液体:顶空气相色谱法测定[J].中国医药工业杂志,2015,46(10):1119-1121.ZHANG Su-juan,ZHANG Xu,YANG Li-xia,et al.Determination of residual organic solvents in sorafenib tosylate by ionic liquids-headspace-gas chromatography[J].Chinese Journal of Pharmaceuticals,2015,46(10):1119-1121.
[10]李肖锋,孔双泉,翟志芳,等.气相色谱法测定牛纤维蛋白原中磷酸三丁酯残留量[J].中国生物制品学杂志,2015,28(6):645-647.LI Xiao-feng,KONG Shuang-quan,ZHAI Zhi-fang,et al.Determination of residual tributyl phosphate content in bovine fibrinogen by gas chromatography[J].Chinese Journal of Biologicals,2015,28(6):645-647.
[11]陈文丽,杨鹏,俞利林,等.顶空毛细管气相色谱法测定奥拉西坦中乙醇、二氯甲烷和4-氯乙酰乙酸乙酯的残留量[J].中南药学,2015,13(1):74-76.CHEN Wen-li,YANG Peng,YU Li-lin,et al.HS-GC determination of residues of ethanol,dichloromethane and ethyl 4-chloraacetoacetate in oxiracetam[J].Central South Pharmacy,2015,13(1):74-76.
[12]国家药典委员会.中华人民共和国药典:2015版4部[K].北京:中国医药科技出版社,2015:105-109.National Pharmacopoeia Committee.China Pharmacopoeia:4edition 2015[K].Beijing:China Medical Science Press,2015:105-109.