Effective Chiral Discrimination of Amino Acids through Oligosaccharide Incorporation by Trapped Ion Mobility Spectrometry

Chiral analysis is critical to many research fields due to different biological functions of enantiomers in living systems. Although the use of ion mobility spectrometry (IMS) has become an alternative technology in the area of chiral measurements, there is still a lack of a general chiral selector for IMS-based chiral recognition, especially for small chiral molecules. Here, a new method using oligosaccharides as the chiral selector has been developed to discriminate chiral amino acids (AAs) by trapped ion mobility spectrometry-mass spectrometry (TIMS-MS). We analyzed 21 chiral amino acids, including small molecules (e.g., alanine and cysteine). Our data showed that the use of nonreducing tetrasaccharides was effective for the separation of chiral AAs, which differentiated 21 chiral AAs without using metal ions. By further incorporating a copper ion, the separation resolution could be improved to 1.64 on average, which accounts for an additional 52% improvement on top of the already achieved separation in metal-free analysis. These results indicate that the use of tetrasaccharides is an effective strategy for the separation of AA enantiomers by TIMS. The method developed in this study may open up a new strategy for effective IMS-based chiral analysis.