The use of shift reagents in ion mobility-mass spectrometry: studies on the complexation of an active pharmaceutical ingredient with polyethylene glycol excipients

Gas-phase ion mobility studies of mixtures containing polyethylene glycols (PEG) and an active pharmaceutical ingredient (API), Lamivudine, have been carried out using electrospray ionization-ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry (ESI-IMS-Q-TOF). In addition to protonated and cationised PEG oligomers, a series of high molecular weight ions were observed and identified as non-covalent complexes formed between Lamivudine and PEG oligomers. The non-covalent complex ions were dissociated using collision induced dissociation (CID) after separation in the ion mobility drift tube to recover the protonated Lamivudine free from interfering matrix ions and with a drift time associated with the precursor complex. The potential of PEG excipients to act as ‘shift reagents’, which enhance selectivity by moving the mass/mobility locus to an area of the spectrum away from interferences, is demonstrated for the analysis of Lamivudine in a Combivir formulation containing PEG and Lamivudine