Separation of asparagine, valine and tetraethylammonium ions overlapping in an ion mobility spectrum by clustering with methanol introduced as a modifier into the buffer gas

We introduced methanol into the buffer gas of an ion mobility spectrometer with an electrospray ionization source, coupled to a quadrupole mass spectrometer, and mobilities of selected compounds changed to different extents, depending on their structures, due to the formation of slow ion–methanol clusters. This differential change in ion mobility was applied to the baseline separation of a mixture of valine, asparagine, and tetraethylammonium ions (TEA) that overlapped in the mobility spectrum; the drift time of TEA did not increase due to steric hindrance to the attachment of methanol molecules to its positive charge by TEA's four ethyl substituents; the valine ion extensively clustered because its positive charge is more accessible for clustering with methanol and, therefore, its drift time increased the most, allowing resolution from TEA and asparagine; asparagine had an intermediate increase in drift time due to the formation of intramolecular bridges that hid the positive charge from methanol molecules and delocalized it; this bridge and clustering made asparagine to show less clustering than valine. Other results show that when the methanol concentration increased from 0.0 to 6.3 mmol m−3, changes in ion mobilities were: −5.0% (valine), −4.2% (phenylalanine), −3.2% (asparagine), −1.5% (glutamine), −1.4% (2,4-lutidine), −0.9% (arginine), −0.3% (2,6-di-tert-butylpyridine, DTBP), −0.2% (tetramethylammonium ion), and 0.0% (other tetraalkylammonium ions). Methanol in the buffer gas produced ion clusters with one to three methanol molecules in compounds with little steric hindrance on the charge as ethanolamine. The introduction of buffer gas modifiers has the potential to be a tool for resolution of complex mixtures in ion mobility spectrometry.