摘要
地平类药物作为二氢吡啶类钙离子通道拮抗剂,在治疗高血压等心血管疾病中有着重要作用,理解这些药物的质谱裂解途径对于研究其在复杂基体中的代谢过程至关重要。本工作采用电喷雾-碰撞诱导解离串联质谱(ESI-CID-MS/MS)技术研究非洛地平、苯磺酸氨氯地平和硝苯地平等地平类药物的质谱裂解行为,揭示裂解反应机理,并总结这类药物的基本裂解规律。结果表明,这些地平类药物在裂解过程中主要发生丢失支链基团反应(例如,丢失HCl或CO+CH_(3)OH等)、质子迁移反应、脱水反应以及去氢芳构化反应。其中,去氢芳构化反应尤为重要,其产生的离子可以作为识别这类药物的特征诊断离子。本研究不仅准确解析了地平类药物去氢芳构化反应的过程,而且为这类药物的精准鉴定和快速检测提供了有效指导,为地平类药物代谢通路的相关研究提供了重要的理论依据。
Dipine drugs,classified as dihydropyridine calcium channel antagonists,are widely utilized in clinical settings as antihypertensive vasodilator calcium antagonist to treat angina pectoris,hypertension,and coronary artery diseases.Commonly used dipine drugs,including felodipine,amlodipine besylate,and nifedipine,can effectively regulate blood pressure levels,increase blood flow to the heart and blood vessels,and thus aid in reducing blood pressure.Additionally,dipine drugs have been used in treatment for Alzheimer’s disease and are known to provide protective effect on the liver.Understanding the fragmentation pathways during mass spectrometry ionization is crucial for studying their metabolic pathways.In this study,the fragmentation behaviors of felodipine,amlodipine besylate,and nifedipine were investigated using electrospray ionization-mass spectrometry coupled to collision-induced dissociation(ESI-CID-MS/MS).Through detailed analysis,the fragmentation characteristics of these dipine drugs were elucidated.It was observed that common reactions under the target ion mode include dehydrogenation,proton migration,dehydration,and the loss of branched chain groups.A key finding of this study is the dehydroaromatization process during the fragmentation of dipine drugs.In this process,the fragment ions generated through dehydroaromatization can serve as characteristic diagnostic markers for identifying dipine drugs.Under the high-energy conditions,dipine molecules undergo complex rearrangements,leading to the conversion of saturated carbon-carbon bonds into unsaturated aromatic ring structures.This transformation alters the chemical properties of the drug molecules and represents the primary fragmentation pathway of dipine drugs.Moreover,dehydroaromatization offers valuable insights into the in vivo metabolic conversion of these drugs,which may occur under the influence of drug-metabolizing enzymes.This conversion can potentially affect both the efficacy and safety of dipine drugs,highlighting the importance of understanding this process for therapeutic use.This study not only provides a method for identifying fragment ions but also establishes a theoretical framework for comprehending the fragmentation pathways of dipine drugs.
作者
王晓云
袁艳春
段敏敏
丁健桦
张小平
WANG Xiao-yun;YUAN Yan-chun;DUAN Min-min;DING Jian-hua;ZHANG Xiao-ping(Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation,East China University of Technology,Nanchang 330013,China)
出处
《质谱学报》
北大核心
2025年第2期187-195,I0003,共10页
Journal of Chinese Mass Spectrometry Society
基金
国家自然科学基金(22164002)
江西省自然科学青年基金(20232BAB213047)
东华理工大学实践教学项目(DHSY-202315)
江西省大学生创新创业训练计划项目(202310405004X)。
