三个候选者,两个峰值:解决与DMS-UVPD相冲突的芬太尼尔原体的分配问题
Christian Ieritano1,2, Allison N Fry3, James N Dodds3
1Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.
概括
芬太尼类似物显示出由于质子化位点的两个峰值. 这项研究证实,主要峰值是piperidine-N质子化,次要峰值是carbonyl-O质子化,解决了药物分析中长期存在的问题.
科学领域:
- 分析化学 分析化学
- 法医化学 法医化学
- 物理化学 物理化学
背景情况:
- 芬太尼的类似物,其特点是皮佩里丁-4-碳胺核心,在低场离子移动谱仪 (IMS) 中表现出双峰.
- 这些峰值归因于原型异构体 (原构体),主要峰值与piperidine质质突变有关.
- 小峰的起源仍在争论中,之前的假设包括胺或碳酸氧质突变.
研究的目的:
- 为了最终解决因芬太尼尔类似物中观察到的双重IMS峰值而导致的质子位点.
- 通过使用先进的分析技术和计算方法的结合,研究十种芬太尼类型的原始体格局.
- 阐明影响不同质体形式形成和稳定性的因素.
主要方法:
- 差分移动光谱法 (DMS) 与紫外线光解离法 (UVPD) 和双重质谱法 (DMS-MS2/MS3) 相结合.
- 量子化学计算,包括用于紫外线吸收光谱的in silico垂直梯度弗兰克-康登 (VGdakFC) 模拟.
- 碰撞横截面 (CCS) 测量和微溶解研究.
主要成果:
- 碎片化路径分析证实,主要的IMS峰值来自于piperidine-N质子,小峰值来自于amide-carbonyl-O质子.
- 计算的CCS值与N和O原体的实验数据密切匹配,而胺-N原体计算显示出显著的偏差.
- 微溶解研究表明,溶剂桥梁缩小了质体之间的能量差距,这表明在电喷离子化过程中O-质子化形式的动力捕获.
结论:
- 这项研究明确地将芬太尼类 analog 的小 IMS 峰值与碳-O 质突赋值,解决了分析中的关键模两可.
- 这些发现凸显了考虑原质子分布及其稳定性在质子分子离子运动谱学中的重要性.
- 了解这些原体平衡对于在法医和分析应用中准确识别和表征芬太尼类似物至关重要.
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