In the host-guest chemistry, formation of targeted complex has attracted considerable attention for many years, especially in metabolomics and pharmacology, which request precise complexation to carry out proper function. Chiral recognition is a widely known example of targeted complexation, which bases on the different interaction between host and small guest molecules that possess insignificant structural differences. Meanwhile, host-guest interaction depending on the protonation sites in a single molecule has not been much of interest so far. In the present work, we confirmed the existence of two different imipramine protomers, distinguished by different host-guest interaction with cucurbit[7]uril (CB[7]). Imipramine is a well-known anti-depression drug containing two nitrogen atoms that can be protonated, each located in a cycloheptadiene ring and side chain. Two complexes of imipramine-CB[7] are clearly observed by ion mobility spectrometry-mass spectrometry, showing two distinctive collision cross section (CCS) values. A few possible structures of complexes are predicted by density functional theory (DFT) calculation, which is in line with the measured CCS trend. Moreover, collision induced dissociation (CID) pattern of targeted complex showed the evidence of both inclusion and exclusion complexes exist in gas phase. Based on the complex structures and their binding affinities suggested by DFT calculation, we conclude that two imipramine inclusion/exclusion complexes are produced either in solution or gas phase, respectively. NMR spectrum of imipramine and CB[7] sample further proved CB[7]-imipramine inclusion complex are derived from solution phase.