Adduct-ion formation in trapped ion mobility spectrometry as a potential tool for studying molecular structures and conformations

Recent developments in the field of ion mobility spectrometry provide new possibilities to explore and understand gas-phase ion chemistry. In this study, hyphenated trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) was applied to investigate analyte ion mobility as function of adduct ion formation for twelve pharmaceutically relevant molecules, and for tetrahydrocannabinol (THC) and its isomer cannabidiol (CBD). Samples were introduced by direct infusion and ions were generated with positive electrospray ionization (ESI+) observing protonated and sodiated ions. Measurements were performed with and without addition of cesium-, lithium-, silver- and sodium ions to the samples. For the tested compounds, metal adduct ions with the same m/z but with different mobility and collision cross section (CCSs) were observed, indicating different molecular conformations. Formation of analyte dimers was also observed, which could be associated with molecular geometry of the compounds. By optimizing the range and speed of the electric field gradient and ramp, respectively, the separation of THC and CBD was achieved by employing the adduct formation. This study demonstrates that the favorable resolution of TIMS combined with the ability to detect weakly bound counter ions is a valuable means for rapid detection, separation and structural assignment of molecular isomers and analyte conformations.