Application of open port sampling interface mass spectrometry (OPSI-MS) to deuterium exchange as an aid for structural elucidation

Andrew D Ray; Graeme Clemens; Stephen W Holman

doi:10.1002/rcm.8536

Application of open port sampling interface mass spectrometry (OPSI-MS) to deuterium exchange as an aid for structural elucidation

Rapid Commun Mass Spectrom. 2021 Apr:35 Suppl 2:e8536. doi: 10.1002/rcm.8536. Epub 2020 Feb 8.

Authors

Andrew D Ray¹, Graeme Clemens², Stephen W Holman²

Affiliations

¹ Global Product Development, Pharmaceutical Technology & Development, AstraZeneca, Macclesfield Campus, Macclesfield, SK10 2NA, UK.
² Chemical Development, Pharmaceutical Technology & Development, AstraZeneca, Macclesfield Campus, Macclesfield, SK10 2NA, UK.

PMID: 31336014
DOI: 10.1002/rcm.8536

Abstract

Rationale: Deuterium exchange has been demonstrated to provide additional information to accurate mass measurement and collision-induced dissociation on unknown chemical structures. An enhanced method for rapid deuterium exchange could make this technique more routine for structural elucidation. Open port sampling interface mass spectrometry (OPSI-MS) with an aprotic solvent offers a rapid method for performing deuterium incorporation.

Methods: Samples of standard drug molecules have been analysed by OPSI-MS directly from solids using a make-up flow of acetonitrile + 0.1% trifluoroacetic acid. The resultant spectra were compared with those obtained by OPSI-MS analysis of the samples dissolved in deuterium oxide (D₂ O). Solutions of these molecules in acetonitrile/D₂ O were analysed using an Atmospheric Solids Analysis Probe (ASAP) at different temperatures to compare the suitability of this technique.

Results: The number of exchangeable hydrogens was obtained through deuterium exchange using the OPSI source, although there was some incomplete exchange or back-exchange observed. Molecules with one to five exchangeable hydrogens were successfully analysed. ASAP analysis produced more complicated spectra with higher levels of incomplete or back-exchanged ions; this was more pronounced at higher temperatures.

Conclusions: The use of OPSI provides a method for the rapid determination of the number of exchangeable hydrogens within a molecule. This yields useful information as an aid to the structural elucidation of unknowns. ASAP produces incomplete exchange and cannot be used for incorporation studies.