Critical Comparison of Liquid Chromatography Coupled to Mass Spectrometry and Three Different Ion Mobility Spectrometry Systems on Their Separation Capability for Small Isomeric Compounds

The very fast separation and identification of isomeric small substances with a molecular weight under 800Da is still a challenge for high-throughput analysis. Inadequate chromatographic or spectrometric separation hampers an unequivocal identification of isomers, which may be recorded as a sum parameter. Reversed-phase liquid chromatography can be considered a generic method for the separation of isomers. However, a separation is usually achieved within minutes and not milliseconds as is typical for ion mobility spectrometry. The aim of this study, therefore, was to investigate the potential of IMS to separate small isomeric compounds. Hence, 23 substances divided into 11 isomeric groups have been selected. Among them, cancer drugs, hormones, pain relievers and others are contained. Three ion mobility spectrometers with different separation principles were compared with respect to their resolving performance. These systems comprised a traveling wave ion mobility spectrometer, a differential ion mobility spectrometer and a differential mobility analyzer. For reference, the chromatographic resolution and peak capacity was determined by high-performance liquid chromatography using a reversed phase.