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

203 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.
@article{3beca41ee1b34fcf9472fc5bfa715f4d,
title = "Structural characterization of drug-like compounds by ion mobility mass spectrometry: Comparison of theoretical and experimentally derived nitrogen collision cross sections",
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 {\AA} 2 and the helium collision cross-section (ω He) range of 63.0-178.8 {\AA} 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 {\AA} 2, respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in ωN 2 value by only 1 {\AA} 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.",
author = "Iain Campuzano and Bush, {Matthew F.} and Robinson, {Carol V.} and Claire Beaumont and Keith Richardson and Hyungjun Kim and Kim, {Hugh I.}",
year = "2012",
month = "1",
day = "17",
doi = "10.1021/ac202625t",
language = "English",
volume = "84",
pages = "1026--1033",
journal = "Industrial And Engineering Chemistry Analytical Edition",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Structural characterization of drug-like compounds by ion mobility mass spectrometry

T2 - Comparison of theoretical and experimentally derived nitrogen collision cross sections

AU - Campuzano, Iain

AU - Bush, Matthew F.

AU - Robinson, Carol V.

AU - Beaumont, Claire

AU - Richardson, Keith

AU - Kim, Hyungjun

AU - Kim, Hugh I.

PY - 2012/1/17

Y1 - 2012/1/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84862909014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862909014&partnerID=8YFLogxK

U2 - 10.1021/ac202625t

DO - 10.1021/ac202625t

M3 - Article

VL - 84

SP - 1026

EP - 1033

JO - Industrial And Engineering Chemistry Analytical Edition

JF - Industrial And Engineering Chemistry Analytical Edition

SN - 0003-2700

IS - 2

ER -