Quantitation of Enantiomeric Excess in an Achiral Environment Using Trapped Ion Mobility Mass Spectrometry.

Abstract

We present a novel, straightforward method to determine the enantiomeric excess (ee) of tryptophan (Trp) and N-tert-butyloxycarbonyl-O-benzylserine (BBS) solutions without chiral additives. For this, lithium carbonate, sodium carbonate, or silver acetate was added to solutions of Trp or BBS. Singly negatively charged dimer and trimer clusters were then formed by electrospray ionization and analyzed using trapped ion mobility spectrometry (TIMS) and time-of-flight mass spectrometry. When a solution contains both enantiomers, homo- and heterochiral clusters are generated which can be separated in the TIMS-tunnel based on their different mobilities using a nitrogen buffer gas. The ratio of homochiral to heterochiral clusters shows a binomial distribution and can be calibrated with solutions of known ee to yield ee measurements of samples with better than 1% accuracy. Samples can be prepared rapidly, and measurements are completed in less than 5 min. Current instrumental limitations restrict this method to rigid molecules with large functional groups adjacent to the chiral centers. Nevertheless, we expect this method to be applicable to many pharmaceuticals and provide the example of 1-methyltryptophan to demonstrate this.