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 language | English |
|---|---|
| Pages (from-to) | 1026-1033 |
| Number of pages | 8 |
| Journal | Analytical chemistry |
| Volume | 84 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2012 Jan 17 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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 -