Synthetic Small Molecule Characterization and Isomer Discrimination Using Gas-Phase Hydrogen–Deuterium Exchange IMS-MS

Ion mobility spectrometry–mass spectrometry (IMS-MS) combined with gas-phase hydrogen–deuterium exchange has been used to characterize novel psychoactive substances (NPSs) which are small synthetic compounds designed to mimic the effects of other illicit substances. Here, NPSs containing labile heteroatom hydrogens were evaluated for HDX reactivity in the presence of either deuterated water (D 2 O) or ammonia (ND 3 ) within the drift tube. An initial evaluation of exchange propensity was performed for six NPSs. Five compounds exchanged in the presence of ND 3 while only one NPS (benzyl piperazine) exchanged with D 2 O. The exchange mechanism of D 2 O requires stabilization with a nearby charged site; the diamine ring of benzyl piperazine provided this charge site at a fixed length. Three disubstituted benzene isomers ( o -, m -, and p -fluorophenyl piperazine) containing the diamine ring structure and a fluorine atom were subsequently analyzed. Having identical isotopic composition and nearly identical drift time distributions, these isomers could not be distinguished by IMS-MS alone. However, upon undergoing HDX in the drift tube, a t test of means (α = 0.05) showed that discrimination was possible if the exchange data from both reagent gases were included. Molecular dynamics simulations show that the proximity of the fluorine to the diamine ring hinders the dihedral angle rotation between the benzene and the diamine ring; this may partially account for the observed exchange differences.