柱前手性衍生化-反相高效液相色谱法拆分布洛芬对映异构体
|
摘要
目的:建立一种柱前手性衍生化-反相高效液相色谱紫外法检测布洛芬的异构体。方法:以N'N-羰基二咪唑(CDI)作为活化剂活化布洛芬的羧基基团,再以(R)-(+)-1-(1-萘基)乙胺(R-NEA)作为手性衍生化试剂进行反应。选用Kromasil C18色谱柱,流速1.0 mL·min~(-1),柱温30℃,以乙腈-0.05%磷酸(68∶32)为流动相,检测波长225 nm。结果:布洛芬的非对映异构体色谱峰的保留时间分别为25.6 min和27.9 min。结论:本方法操作简单,条件温和,衍生化产物稳定,且衍生化试剂价格便宜,更准确地实现了对布洛芬对映异构体的分离检测。
Objective:To establish a pre-column chiral derivatisation method for determination of the ibuprofen enantiomers based on HPLC.Methods:The carboxylic acid of ibuprofen was activated with CDI as an activator.The activated ibuprofen was resolved for HPLC via chiral derivatization with reagent R-naphthylethylamine(R-NEA).The optimal chromatographic conditions were as follows:Kromasil C18column(4.6 mm×250 mm,5 μm),detection wavelength:225 nm,flow rate:1.0 mL·min~(-1),mobile phase:acetonitrile-0.05% phosphoric acid solution(68∶32).Results:The retention times of(R) and(S)-enantiomers were 25.6 min and 27.9 min,respectively.Conclusion:The method has the advantages of simple operation,mild condition,stable products of derivatization and low cost of derivatization reagent.This method is more accurate to realize the detection of the enantiomers of ibuprofen.
Objective:To establish a pre-column chiral derivatisation method for determination of the ibuprofen enantiomers based on HPLC.Methods:The carboxylic acid of ibuprofen was activated with CDI as an activator.The activated ibuprofen was resolved for HPLC via chiral derivatization with reagent R-naphthylethylamine(R-NEA).The optimal chromatographic conditions were as follows:Kromasil C18column(4.6 mm×250 mm,5 μm),detection wavelength:225 nm,flow rate:1.0 mL·min~(-1),mobile phase:acetonitrile-0.05% phosphoric acid solution(68∶32).Results:The retention times of(R) and(S)-enantiomers were 25.6 min and 27.9 min,respectively.Conclusion:The method has the advantages of simple operation,mild condition,stable products of derivatization and low cost of derivatization reagent.This method is more accurate to realize the detection of the enantiomers of ibuprofen.
引文
[1]Noctor TAG,Felix G,Wainer IW.Stereochemical resolution of enantiomeric 2-aryl propionic acid nonsteroidal anti-inflammatory drugs on a human serum albumin based high-performance liquid chromatographic chiral stationary phase[J].Chromatographia,1991,31(1):55-9.
[2]Mehvar R,Jamali F,Pasutto FM.Liquid-chromatographic assay of ibuprofen enantiomers in plasma[J].Clin Chem,1988,34(3):493-6.
[3]阎建辉,盛盈,黄可龙,等.手性溶剂萃取分离布洛芬对映体[J].化工学报,2007,58(3):679-84.
[4]Bhushan R,Parshad V.Resolution of(+/-)-ibuprofen using L-arginine-impregnated thin-layer chromatography[J].J Chromatogr A,1996,721(2):369-72.
[5]Engstrom KM,Sheikh A,Ho R,et al.The stability of N,N-Carbonyldiimidazole toward atmospheric moisture[J].Org Process Res Dev,2014,18(4):488-94
[6]杨凤玲,温金梅.羰基二咪唑[J].精细与专用化学品,2003,11(1):20.
[7]Woodman EK,Chaffey JGK,Hopes PA,et al.N,N′-Carbonyldiimidazole-mediated amide coupling:significant rate enhancement achieved by acid catalysis with imidazole center dot HCl[J].Org Process Res Dev,2009,13(1):106-13.
[8]涂昌位,臧阳陵,李萍,等.医药中间体N,N′-羰基二咪唑的合成研究[J].精细化工中间体,2001,31(2):33-4.
[9]Germershaus O,Pickaert G,Konrad J,et al.Imidazole and dimethyl aminopropyl-functionalized hyperbranched polymers for nucleic acid transfection[J].Macromol Biosci,2010,10(9):1055-62.
[10]Verma SK,Ghorpade R,Pratap A,et al.Solvent free,N,N′-carbonyldiimidazole(CDI)mediated amidation[J].Tetrahedron Lett,2012,53(19):2373-6.
[2]Mehvar R,Jamali F,Pasutto FM.Liquid-chromatographic assay of ibuprofen enantiomers in plasma[J].Clin Chem,1988,34(3):493-6.
[3]阎建辉,盛盈,黄可龙,等.手性溶剂萃取分离布洛芬对映体[J].化工学报,2007,58(3):679-84.
[4]Bhushan R,Parshad V.Resolution of(+/-)-ibuprofen using L-arginine-impregnated thin-layer chromatography[J].J Chromatogr A,1996,721(2):369-72.
[5]Engstrom KM,Sheikh A,Ho R,et al.The stability of N,N-Carbonyldiimidazole toward atmospheric moisture[J].Org Process Res Dev,2014,18(4):488-94
[6]杨凤玲,温金梅.羰基二咪唑[J].精细与专用化学品,2003,11(1):20.
[7]Woodman EK,Chaffey JGK,Hopes PA,et al.N,N′-Carbonyldiimidazole-mediated amide coupling:significant rate enhancement achieved by acid catalysis with imidazole center dot HCl[J].Org Process Res Dev,2009,13(1):106-13.
[8]涂昌位,臧阳陵,李萍,等.医药中间体N,N′-羰基二咪唑的合成研究[J].精细化工中间体,2001,31(2):33-4.
[9]Germershaus O,Pickaert G,Konrad J,et al.Imidazole and dimethyl aminopropyl-functionalized hyperbranched polymers for nucleic acid transfection[J].Macromol Biosci,2010,10(9):1055-62.
[10]Verma SK,Ghorpade R,Pratap A,et al.Solvent free,N,N′-carbonyldiimidazole(CDI)mediated amidation[J].Tetrahedron Lett,2012,53(19):2373-6.