To enhance the performance of charge-detection mass spectrometry, we investigated the behaviour of macromolecular single ions on their paths towards and within the Orbitrap analyser. Ions with a mass beyond one megadalton reach a plateau of stability and can be successfully trapped for seconds, travelling a path length of multiple kilometres, thereby enabling precise mass analysis with an effective resolution of greater than 100,000 at a mass-to-charge ratio of 35,000. Through monitoring the frequency of individual ions, we show that these high-mass ions, rather than being lost from the trap, can gradually lose residual solvent molecules and, in rare cases, a single elementary charge. We also demonstrate that the frequency drift of single ions due to desolvation and charge stripping can be corrected, which improves the effective ion sampling 23-fold and gives a twofold improvement in mass precision and resolution.