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雷贝拉唑钠及其氘代产物的核磁共振谱及电喷雾质谱分析

Analysis of rabeprazole sodium and its deuterated product by NMR and ESI-MS
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摘要 目的:对雷贝拉唑钠1H、13C-NMR谱的谱峰进行归属,研究部分质子、碳原子信号随时间变化的规律,获得雷贝拉唑钠的核磁共振谱图特征;通过对雷贝拉唑钠及其在氘代溶液中形成的产物的质谱数据的分析,获得相关化合物的碎片裂解规律。方法:将适量雷贝拉唑钠分别溶解在d6-DMSO、CD3OD中,在不同的时间段采集1H、13C-NMR信号;利用电喷雾质谱(ESI-MS)对雷贝拉唑钠及其在氘代试剂中形成的产物进行全扫描和二级质谱分析。结果:NMR谱数据显示,在CD3OD溶液体系中,8位亚甲基的1H、13C信号强度随着溶液放置时间延长而逐渐减弱,ESI-MS的全扫描质谱显示雷贝拉唑钠在氘代溶液中形成了氘代产物,二级质谱碎片丢失特征显示,在正离子模式下,雷贝拉唑钠及其氘代产物的二级质谱均存在如下的断裂特征:8位亚甲基与亚砜基之间的烯醇式互变异构形成CH=S-OH键,然后丢失一个H2O(或HOD)分子碎片。这个特征有助于解释在氘代甲醇溶液中,8位亚甲基氢发生的氘代现象。结论:雷贝拉唑钠结构中8位亚甲基氢比较活泼,在CD3OD体系中容易发生H/D交换。该实验结果对具有相似结构的质子泵药物的钠盐的结构分析有重要的借鉴意义。 Objective: To obtain 1H、13C-NMR characters of rabeprazole sodium dissolved in CDOD3 and d 6-DMSO.To investigate the changes of signal response of part 1H and 13C atom spectrometry with the time variation.To study the fragmentation pathway of rabeprazole sodium and its deuterated product by illustrating the electrospray ionization mass(ESI-MS)data.Method:Rabeprazole sodium was dissolved in d 6-DMSO and CD3OD respectively.1H-NMR and 13C-NMR data were collected at different time points.ESI-MS was used to investigate the mass characters of rabeprazole sodium and its deuterated product under the modes of full scan and MS2.Results: The signal responses of the 1H and 13C-NMR for 8-methylene of rabeprazole sodium gradually reduced with time extension.The ESI-MS full scan spectrometry characters confirmed that deuterated products were produced when rabeprazole sodium was dissolved in deuterated solvents.The ESI-MS2 spectrometry characters of rabeprazole sodium and its deuterated product indicated that CH=S-OH would be formed between 8-methylene and sulfoxide through enol tautomerism,and then loss of H2O(or HOD)fragment occurred.These results would help us to explain the deuterated process of 8-methylene hydrogen in CD3OD solution system.Conclusion: The 8-methylene hydrogen of rabeprazole sodium was relatively active and prone to H/D exchange when dissolved in CD3OD.Results of the present study provide a comprehensive reference for the structural analysis of the sodium salt of proton pump drugs with similar structure of rabeprazole sodium.
出处 《药物分析杂志》 CAS CSCD 北大核心 2013年第4期551-556,共6页 Chinese Journal of Pharmaceutical Analysis
基金 广州地区分析测试基金专题(No:201004)
关键词 雷贝拉唑钠 质子泵抑制剂 电喷雾质谱 核磁共振谱 H D交换 烯醇式互变异构 活泼氢 rabeprazole sodium proton pump inhibitors ESI-MS NMR H/D exchange enol tautomerism active hydrogen
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参考文献8

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