Exploration of chiral drugs as references for chiral discrimination of valsartan and voriconazole by tandem mass spectrometry

The use of mass spectrometry for chiral recognition and quantification has attracted great interest owing to its speed, sensitivity, specificity, and tolerance. However, searching for chiral selectors in chiral analyses using mass spectrometry is still problematic. In this study, chiral drugs could be applied as references for the chiral recognition and enantiomeric quantification of valsartan and voriconazole. Two novel pairs of metal-bound diastereomeric complex ions were detected by mass spectrometry, namely, nickel (II)-bound dimeric ions Ni^II (2R,5S-emtricitabine) (S-valsartan)-H]⁺ and Ni^II (2R,5S-emtricitabine) (R-valsartan)-H]⁺ and copper (II)-bound dimeric ions Cu^II (S,S,S-enalaprilat) (2S,3R-voriconazole)-H]⁺ and Cu^II (S,S,S-enalaprilat) (2R,3S-voriconazole)-H]⁺. The resulting diastereomers were successfully identified based on the relative intensities of their characteristic fragments using tandem mass spectrometry. The logarithm of the characteristic fragment ion abundance ratio exhibited a good linear relationship with the enantiomeric excess. Density functional theory calculations were also performed to elucidate the mechanism of the structural differences observed in the MS results. This established approach proves that chiral drugs can serve as ligands for the rapid recognition and quantitative analysis of other chiral drugs without a chiral chromatographic column or complex sample pretreatment.