Determination of enantiomeric compositions of DOPA by tandem mass spectrometry using the kinetic method with fixed ligands

Abstract

A fixed ligand (FL) version of the kinetic method was applied to rapid, simple, and accurate chiral analysis of DOPA, which is an important drug used for treatment of Parkinson's disease. Singly charged clusters containing the transition metal ion Cu(II), pyridyl ligands which serve as a fixed ligand, some amino acid as a reference, and the analyte DOPA were generated by electrospray ionization. The cluster ion of interest was mass-selected, and the kinetics of its competitive unimolecular dissociations was investigated in an ion trap mass spectrometer. The chiral selectivity (R(chiral)), the ratio of the two fragment ion abundances when the cluster contains one pure enantiomer of the analyte expressed relative to that for the other enantiomer, varies with fixed ligands, references, and transition metals. Chiral discrimination was optimized in 1,10-phenanthroline as a FL, L-Phe and L-Pro as a reference, and Cu(II) as a central metal ion. Quantitative determinations of the enantiomeric composition of DOPA were achieved using two-point calibration curves. The linear relationship between the logarithm of the fragment ion abundance ratio (ln R) and enantiomeric compositions (ee%) of the DOPA allows the determination of the chiral purity of enantiomeric mixtures.

Enantiomer assays of amino acid derivatives using tertiary amine appended trans-4-hydroxyproline derivatives as chiral selectors in the gas phase

“…Quantitative analysis of enantiomeric composition can also be performed based on the calibration curve constructed by using enantiomeric mixtures of known enantiomeric excess [25]. Different groups have reported a variety of chiral recognition systems using various chiral references and transition metal ions [6,[44][45][46].…”

Chiral detection of entecavir stereoisomeric impurities through coordination with R‐besivance and ZnII using mass spectrometry

“…It is clear that MS possesses advantages such as rapid analysis, high sensitivity, and reduced sample consumption; it also does not necessitate isotope labeling or other derivatization treatment to analytes. Currently, there are 4 major types of MS techniques used in chiral recognition: (1) the host‐guest method, (2) ion/molecule (equilibrium) reactions, (3) collision‐induced dissociation of diastereomeric complex (which includes the kinetic method [KM], the fixed ligand KM, and the chiral recognition ratio method) and (4) ion mobility MS . The most commonly used type is KM because the experimental data interpretation is much easier because only the relative abundances of 2 fragment ions are needed and isomer separation is not necessary.…”

Isomeric Distinction of Small Oligosaccharides: A Bottom-Up Approach Using the Kinetic Method

“…O riginally developed for the determination of thermochemical properties of molecules in the gas phase [1], the kinetic method was further successfully utilized to differentiate and quantify enantiomers in mixture, such as amino acids [2][3][4][5], sugars [6], chiral drugs [7][8][9][10][11], and hormones [12]. For the same classes of compounds, the kinetic method has also proven relevant for the distinction of isomers, as reported for peptides [13][14][15][16] and amino acids [17], monosaccharides [18] and thyroid hormones [19].…”