Discrimination of Lutidine Isomers by Ion Mobility Spectrometry Using α-Cyclodextrin and Metal Ions

The identification and separation of isomers are of great significance due to the distinct physicochemical properties and wide-ranging applications. In this study, a simple and rapid method based on ion mobility spectrometry (IMS) was developed to distinguish and relatively quantify the 2,5/3,5-lutidine (2,5/3,5-LUT) isomers. Initially, the two isomers were separated through complexation with α-, β-, and γ-cyclodextrins (CDs), with a slight inter-peak resolution observed in the formation of the [CD+LUT+H]⁺ complexes. To enhance the differentiation, metal ions (Mn²⁺, Fe²⁺, Co²⁺, Zn²⁺) were introduced to form ternary complexes, and α-CD in coordination with Zn²⁺ yielded the most effective separation of 2,5/3,5-LUT. Theoretical conformations of [α-CD + 2,5/3,5-LUT+H]⁺ and [α-CD + 2,5/3,5-LUT+Zn-H]⁺ were optimized. Furthermore, collision-induced dissociation (CID) analysis of the [α-CD + 2,5/3,5-LUT+Zn-H]⁺ complexes revealed that the dissociation energy varies due to different spatial conformations. Finally, the method demonstrated reliable relative quantification, achieving a satisfactory linear correlation (<i>R</i>²&gt;0.99). The developed approach offers a simple, precise, and cost-effective strategy for isomer identification and conformational analysis, with potential applications in chemical and pharmacological fields.