Structural elucidation and quantitative analysis of cinnamic acid derivatives using TIMS-MS, cyclodextrin adducts, and computational chemistry

This study developed a rapid TIMS-MS method combined with computational chemistry to differentiate and quantify three groups of cinnamic acid derivative (CAD) isomers: 2/4- hydroxycinnamic acid (2/4-HCA), α/β-methylcinnamic acid (α/β-MCA), and o/m/p- Methoxycinnamic acid (o/m/p-MCA). Separation leveraged distinct non-covalent complexes formed with α−/β−/γ-cyclodextrin (CDs) and metal ions. Optimal conditions achieved excellent resolution (R p-p up to 1.05), particularly for [2/4-HCA + α-CD + Mg-H] + and [o/m/p-MCA + α-CD + Mg-H] + complexes. Computational analysis confirmed the conformational differences and non-covalent interaction sites enabling separation, aligning well with experiments (error ≤ 3.46%). The method showed high sensitivity of limit of detection (LOD) ≤3.27 ng·mL −1 , linearity (R 2  > 0.99), and successfully quantified CAD isomers in pineapple leaves and cinnamon powder with good recovery (≥80.60%) and precision of relative standard deviation (RSD ≤5.75%). By avoiding chemical derivatization and chromatographic separation, our method provides a rapid and simple platform for the direct analysis of bioactive food components, demonstrating great promise for food quality control.