Improvements in quantitative chiral determinations using the mass spectrometric kinetic method

Abstract

A significant shortcoming of the kinetic method for determining chiral purity from the competitive dissociation of a metal complex chelated with a chiral analyte and chiral reference is that it does not give useful quantitative data for high purity chiral samples in comparison to the standard chiral chromatography techniques. To extend the range of applications of the kinetic method to high chiral purity samples, a “vernier” method is reported which gives more accurate quantitative data for samples covering a narrow range of chiral purity. This is demonstrated for the case of a model amino acid in which Ni II is used as the metal cation, asparagine as the chiral reference, and the analyte is tryptophan. By selecting experimental conditions to give a measured peak abundance ratio near unity for the two competitive fragments (where abundance ratios are more accurately measured than at higher or lower values), samples of high (90–100%) chiral purity were more accurately assayed in the experiment using pure tryptophan. By switching the chirality of the reference compound, samples in the low (0–10%) chiral purity range could also be more precisely measured. The quantitative improvement in accuracy of the chiral measurement is shown by the average accuracy of 0.51% deviation (for the 90–100% chiral purity range of tryptophan using l-Asn as chiral reference) in comparison to the average deviation of 104.1% in the non-vernier region (the region that falls outside the high accuracy region of interest).