Soft-Chain-Induced Ultrahigh-Resolution Chiral Separation of Amino Acids via Bimetallic Immobilization in MALDI-TIMS-MS

As bioactive compounds, chiral amino acids (AAs) have been demonstrated to play pivotal roles in different physiological processes, thereby influencing human health. The assessment of the relative enantiomeric ratio through analytical methods is essential for indicating the abnormal status of disease progression, which drives the development of effective methods for resolving and identifying enantiomers. This work presents a robust strategy for the ultrahigh-resolution analysis of chiral AAs using MALDI-TIMS-MS. By employing a chiral derivatization process using S-NIFE and stabilizing the soft chain of the derivatization reagent with bimetal ion addition, the separation of 19 pairs of proteinogenic AAs was successfully achieved. This method not only demonstrates outstanding separation capability but also proves its efficiency in determining enantiomeric ratios, extending its applicability to real sample analysis.