Ion–shift reagent binding energy and the mass–mobility shift correlation in ion mobility spectrometry

Rationale Ion mobility spectrometry (IMS) detects illegal substances and explosives in airports, ports, and customs. This is complicated by false positives caused by overlapping peaks. Shift reagents selectively change ion mobilities through adduction with analyte ions. This discriminates false positives because interferents and illegal substances respond differently to shift reagents. Methods We introduced five different shift reagents using electrospray ionization–IMS–mass spectrometry to study the effect of interaction energy, intermolecular bonds, and analyte size on ion mobility shifts. Analyte ion–shift reagent interactions were calculated using Gaussian. Results The mobility shifts showed a decreasing trend as the molecular weight increased for a series of ten compounds. The shift in drift time better reflected the pure effect of shift reagents. Valinol was an exception to this trend because it had a low binding energy interaction with all shift reagents and, consequently, its clusters were short‐lived. This produced fewer collisions against the buffer gas and a shorter drift time, compared to ions of similar molecular weight. Conclusions The results of this investigation are important for understanding the behavior of shift reagents in resolving overlapping peaks that cause interferences. The suppression of false positives eases the transit of passengers and cargos, increases the confiscation of illicit substances, and saves money and distress due to needless delays in customs and airports.