Isomeric and Conformational Analysis of Small Drug and Drug-Like Molecules by Ion Mobility-Mass Spectrometry (IM-MS).

This chapter provides a broad overview of ion mobility-mass spectrometry (IM-MS) and its applications in separation science, with a focus on pharmaceutical applications. A general overview of fundamental ion mobility (IM) theory is provided with descriptions of several contemporary instrument platforms which are available commercially (i.e., drift tube and traveling wave IM). Recent applications of IM-MS toward the evaluation of structural isomers are highlighted and placed in the context of both a separation and characterization perspective. We conclude this chapter with a guided reference protocol for obtaining routine IM-MS spectra on a commercially available uniform-field IM-MS.

Chiral separation of diastereomers of the cyclic nonapeptides vasopressin and desmopressin by uniform field ion mobility mass spectrometry.

In this study ion mobility-mass spectrometry (IM-MS) is used to distinguish chiral diastereomers of the nonapeptides desmopressin and vasopressin. The differences in gas phase cross sectional area (ca. 2%) were sufficient to directly resolve the enantiomers present in a binary mixture. Results from computational modeling indicate that chiral recognition by IM-MS for nonapeptides is possible due to their diastereomer-specific conformations adopted in the gas-phase, namely a compact ring-tail conformer specific to the l-diastereomer forms.