Department of Chemistry, Yale University, New Haven, CT, 06520, USA.
College of Science and Mathematics, University of the Virgin Islands, St. Thomas, 00802, Virgin Islands (U.S.).
J Am Soc Mass Spectrom. 2017 Nov;28(11):2414-2422. doi: 10.1007/s13361-017-1767-z. Epub 2017 Aug 11.
Recent advances in the coupling of vibrational spectroscopy with mass spectrometry create new opportunities for the structural characterization of metabolites with great sensitivity. Previous studies have demonstrated this scheme on 300 K ions using very high power free electron lasers in the fingerprint region of the infrared. Here we extend the scope of this approach to a single investigator scale as well as extend the spectral range to include the OH stretching fundamentals. This is accomplished by detecting the IR absorptions in a linear action regime by photodissociation of weakly bound N molecules, which are attached to the target ions in a cryogenically cooled, rf ion trap. We consider the specific case of the widely used drug Valsartan and two isomeric forms of its metabolite. Advantages and challenges of the cold ion approach are discussed, including disentangling the role of conformers and the strategic choices involved in the selection of the charging mechanism that optimize spectral differentiation among candidate structural isomers. In this case, the Na complexes are observed to yield sharp resonances in the high frequency NH and OH stretching regions, which can be used to easily differentiate between two isomers of the metabolite. Graphical Abstract ᅟ.
振动光谱与质谱联用的最新进展为代谢物的结构特征提供了极大灵敏度的新机会。先前的研究已经在 300K 离子上使用非常高功率的自由电子激光在红外指纹区域证明了这一方案。在这里，我们将该方法的范围扩展到单个研究人员的规模，并将光谱范围扩展到包括 OH 伸缩基频。这是通过在低温冷却的射频离子阱中，通过弱结合 N 分子的光解，在线性作用状态下检测到 IR 吸收来实现的。我们考虑了广泛使用的药物缬沙坦及其代谢物的两种异构体的具体情况。讨论了冷离子方法的优点和挑战，包括解卷积构象的作用以及在选择最佳荷质比机制方面的战略选择，该机制可以优化候选结构异构体之间的光谱差异。在这种情况下，Na 配合物在高频 NH 和 OH 伸缩区域产生尖锐的共振，可以用于轻松区分代谢物的两种异构体。
