HPLC-QTOF_MS法测定马来酸依那普利及中间体中的对甲苯磺酸乙酯

目的:[HTSS][JP+2]建立HPLC-QTOF MS测定马来酸依那普利及中间体N-[1-(S)-乙氧甲酰基-3-苯丙基]-L-丙氨酸中对甲苯磺酸乙酯的方法。[HTH][STHZ]方法:[STBZ][HTSS]采用Eclipse plus C₁₈色谱柱(3.0 mm×100 mm,1.8 μm),以20 mmol·L^-1甲酸铵水溶液(A)-乙腈(B)为流动相,梯度洗脱(0~2 min,10%→50%B;2~4 min,50%→60%B;4~7 min,60%→90%B;7~8 min,90%B),流速1.0 mL·min^-1,柱温50 ℃;采用正离子模式采集数据。[HTH][STHZ]结果:[STBZ][HTSS]对甲苯磺酸乙酯浓度在0.20~5.01 μg·mL^-1范围内线性关系良好(r=0.9955);日内和日间精密度良好,RSD小于6.7%;定量限和检测限分别为0.4 ng、0.2 ng;马来酸依那普利及中间体回收率(n=9)分别为102.6%和90.8%。[HTH][STHZ]结论:[STBZ][HTSS]本法简便、灵敏,可用于对甲苯磺酸乙酯的定量研究。

Objective:To establish a method of HPLC-QTOF MS to detect ethyl p-toluenesulfonate in enalapril maleate and intermediate.Methods:The method was achieved on a Eclipse plus C₁₈ column(3.0 mm×100 mm,1.8 μm) utilizing a mobile phase of 20 mmol·L^-1 ammonium formate(A)-acetonitrile(B) with gradient elution(0-2 min,10%→50%B;2-4 min,50%→60%B;4-7 min,60%→90%B;7-8 min,90%B) at the flow rate of 1.0 mL·min^-1.And the temperature of column was set at 50 ℃;The data was acquired in positive ion mode.Results: Standard curve was linear in the range of 0.20-5.01 μg·mL^-1(r=0.9955).The values of limit of quantification and limit of detection were 0.4 ng and 0.2 ng,respectively.RSDs for the intra- and inter-day were less than 6.7%.The recoveries(n=9) of ethyl p-toluenesulfonate in enalapril maleate and intermediate were 102.6% and 90.8%,respectively.Conclusion: The method is convenient and sensitive for detecting ethyl p-toluenesulfonate in enalapril maleate and intermediate.

1 de los A Oliva M,Sombra LL,Olsina RA,et al.A new fluorescent assay for enalapril maleate.J Fluoresc,2005,15(5):723
2 Qin XZ,Joe DeMarco,Dominic PI.Simultaneous determination of enalapril,felodipine and their degradation products in the dosage formulation by reversed-phase high-performance liquid chromatography using a Spherisorb C₈ column.J Chromatogr A,1995,707:245
3 Toporii R,Mlakar A,Hvala J,et al.Identication of new impurities of enalapril maleate on oxidation in the presence of magnesium monoperoxyphthalate.J Pharm Biomed Anal,2010,52(2):294
4 Bhardwaj SP,Singh S.Study of forced degradation behavior of enalapril maleate by LC and LC-MS and development of a validated stability-indicating assay method.J Pharm Biomed Anal,2008,46(1):113
5 YIN Guo-zhen(殷国真),GAO Su-ying(高素英).Determination of two constituents in enalapril maleate composite tablets by HPLC(高效液相色谱法测定复方马来酸依那普利片中两组分的含量).Chin J Pharm Anal(药物分析杂志),1996,16(4):227
6 Zhou JL,Li P,Li HJ,et al.Development and validation of a liquid chromatography/ electrospray ionization time-of-flight mass spectrometry method for relative and absolute quantification of steroidal alkaloids in Fritillaria species.J Chromatogr A,2008,1177(1):126