LC-MS法鉴定依普利酮的降解产物  

LC- MS identification of the degradation products of eplerenone

作　　者：杜明荦[1,2] 朱婷婷[1] 苏浩明[1] 张云静[1] 宋敏[1] 杭太俊[1] 

机构地区：[1]中国药科大学,南京210009 [2]河南省食品药品检验所,郑州450003

出　　处：《药物分析杂志》2014年第1期85-90,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:采用高效液相色谱-质谱联用技术鉴定依普利酮的降解产物结构。方法:采用Zorbax Extend C18(250 mm×4.6 mm,5μm)色谱柱,以10 mmol·L-1醋酸铵溶液作为流动相A,以甲醇-乙腈(50∶50)为流动相B,进行梯度洗脱[0 min(70%A-30%B)→8 min(70%A-30%B)→45 min(20%A-80%B)→53 min(20%A-80%B)→55 min(70%A-30%B)→65 min(70%A-30%B)],电喷雾正离子化高分辨TOF/MS和MS/MS检测并解析降解产物结构。TOF/MS雾化气压力345 kPa,温度350℃,干燥气流量10 L·min-1,毛细管电压4 kV,碎片电压100 V,MS/MS测定氩气CID压力0.2 Pa,碰撞能量20 eV。结果:检测到依普利酮的4个降解产物,通过有机反应机制分析和质谱解析鉴定了他们的结构,并结合色谱制备和NMR测定确证了主要降解产物结构。结论:色谱-质谱联用技术能有效地用于有关物质的鉴定,依普利酮降解产物的鉴定结果可为其质量控制提供参考依据。Objective： To identify the degradation products of eplerenone by hyphenated LC-MS methods. Methods： The separation was carried out on a Zorbax Extend C18 column（250 mm×4.6 mm,5 μm） with mobile phase consisting of 10 mmol·L^-1 ammonium acetate solution（A）and methanol-acetonitrile（50： 50）（B）by gradient elution [0 min（70%A-30%B）→8 min（70%A-30%B）→45 min（20%A-80%B）→53 min（20%A-80%B）→55 min（70%A-30%B）→ 65 min（70%A-30%B）].The degradation products were detected by positive ESI high resolution TOF/MS and their MS/MS spectra were determined as well.The conditions of TOF/MS were as follows：nebulizer：345 kPa,gas temperature：350℃, drying gas：10 L·min^-1,capillary voltage：4 kV and fragmentor：100 V.The collision gas pressure of MS/MS was set at 0.2 Pa,and the collision energy at 20 eV. Results： There were 4 degradation products in eplerenone and their chemical structures were speculated through the elucidation of their accurate TOF/MS data of the [H＋H]^＋ ions,the corresponding product MS spectra and further validated with the organic reaction mechanisms.The chemical structure of the main degradation product was also confirmed by preparative LC and NMR analysis. Conclusion： The LC-MS method is useful for the identification of degradation products in pharmaceuticals.The degradation products found in eplerenone are valuable for its quality control.

关 键 词：依普利酮 选择性醛固酮受体拮抗剂 有关物质 降解产物 结构鉴定 液相色谱-质谱联用 核磁共振光谱 

分 类 号：R917[医药卫生—药物分析学]