Structural characterization of drug-like compounds by ion mobility mass spectrometry: Comparison of theoretical and experimentally derived nitrogen collision cross sections

Iain Campuzano, Matthew F. Bush, Carol V. Robinson, Claire Beaumont, Keith Richardson, Hyungjun Kim, Hugh I. Kim

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (ωN 2) range of 124.5-254.3 Å 2 and the helium collision cross-section (ω He) range of 63.0-178.8 Å 2. Absolute ωN 2 and ω He values for the drug-like calibrants and two diastereomers were measured using a drift-tube instrument with radio frequency (RF) ion confinement. T-wave drift-times for the protonated diastereomers betamethasone and dexamethasone are reproducibly different. Calibration of these drift-times yields T-wave ωN 2 values of 189.4 and 190.4 Å 2, respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in ωN 2 value by only 1 Å 2, even though the resolution of these IM experiments were ∼40 (ω/δω). Demonstrated through density functional theory optimized geometries and ionic electrostatic surface potential analysis, the small but measurable mobility difference between the two diastereomers is mainly due to short-range van der Waals interactions with the neutral buffer gas and not long-range charge-induced dipole interactions. The experimental RF-confining drift-tube and T-wave ωN 2 values were also evaluated using a nitrogen based trajectory method, optimized for T-wave operating temperature and pressures, incorporating additional scaling factors to the Lennard-Jones potentials. Experimental ω He values were also compared to the original and optimized helium based trajectory methods.

Original languageEnglish
Pages (from-to)1026-1033
Number of pages8
JournalAnalytical chemistry
Volume84
Issue number2
DOIs
Publication statusPublished - 2012 Jan 17
Externally publishedYes

Fingerprint

Mass spectrometry
Nitrogen
Ions
Pharmaceutical Preparations
Helium
Trajectories
Calibration
Lennard-Jones potential
Betamethasone
Dexamethasone
Spectrometry
Density functional theory
Electrostatics
Buffers
Gases
Molecules
Geometry
Experiments
Temperature

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Structural characterization of drug-like compounds by ion mobility mass spectrometry : Comparison of theoretical and experimentally derived nitrogen collision cross sections. / Campuzano, Iain; Bush, Matthew F.; Robinson, Carol V.; Beaumont, Claire; Richardson, Keith; Kim, Hyungjun; Kim, Hugh I.

In: Analytical chemistry, Vol. 84, No. 2, 17.01.2012, p. 1026-1033.

Research output: Contribution to journalArticle

Campuzano, Iain ; Bush, Matthew F. ; Robinson, Carol V. ; Beaumont, Claire ; Richardson, Keith ; Kim, Hyungjun ; Kim, Hugh I. / Structural characterization of drug-like compounds by ion mobility mass spectrometry : Comparison of theoretical and experimentally derived nitrogen collision cross sections. In: Analytical chemistry. 2012 ; Vol. 84, No. 2. pp. 1026-1033.
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