Quotient ratio method for quantitative enantiomeric determination by mass spectrometry

The quotient ratio (QR) method, a new quantitative method for enantiomeric determination by mass spectrometry, is presented. The method is illustrated by the case in which a chiral analyte (A) and a chiral reference compound (ref*) are simultaneously coordinated to a transition metal ion (e.g., Cu2+ or Zn2 ) to form a singly charged deprotonated cluster ion in the course of electrospray ionization. The trimeric complex ion (three chiral ligands-2 mol of the analyte and 1 mol of the reference compound) is collisionally activated and undergoes dissociation by competitive loss of either a neutral reference or a neutral analyte. The ratio of the product ion branching ratios measured when pure chiral reference compounds (ref*D and ref*L) are employed in separate experiments is related via the kinetic method to the enantiomeric composition of the chiral mixture. This quotient ratio is logarithmically related to enantiomeric purity. In contrast to the previous single ratio method (Tao, W. A.; Zhang, D.; Wang, F.; Thomas, P. D.; Cooks, R. G. Anal. Chem. 1999, 71, 4427), the QR method reported here requires only one sample of the analyte with known optical purity to allow construction of a calibration curve. Accurate determinations of enantiomeric excess for amino acids and the chiral drug DOPA are demonstrated.