Understanding Gas Phase Modifier Interactions in Rapid Analysis by Differential Mobility-Tandem Mass Spectrometry

Abstract

A systematic study involving the use and optimization of gas phase modifiers in quantitative differential mobility- mass spectrometry (DMS-MS) analysis is presented using mucleoside-adduct biomarkers of DNA damage as an important reference point for analysis in complex matrices. Commonly used polar protic and polar aprotic modifiers have been screened for use against two deoxyguanosine adducts of DNA: N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP) and N-(deoxyguanosin-8-y1)-2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (dG-C8-PhIP). Particular attention was paid to compensation voltage (CoV) shifts, peak shapes and product ion signal intensities while optimizing the DMS-MS conditions. The optimized parameters were then applied to rapid quantitation of the DNA adducts in calf thymus DNA. After a protein precipitation step, adduct levels corresponding to less than one modification in 106 normal DNA bases were detected using the DMS-MS platform. Based on DMS fundamentals and ab-initio thermochemical results we interpret the complexity of DMS modifier responses in terms of thermal activation and the development of solvent shells. At very high bulk gas temperature, modifier dipole moment may be the most important factor in cluster formation and cluster geometry in mobility differences, but at lower temperatures multi-neutral clusters are important and less predictable. This work provides a useful protocol for targeted DNA adduct quantitation and a basis for future work on DMS modifier effects.

Solvent vapor effects in planar high-field asymmetric waveform ion mobility spectrometry: Solvent trends and temperature effects

“…Recently published work from this research group focused on initial investigations into solvent vapor effects on FAIMS ion behavior using the aforementioned higher resolving power FAIMS cells [21], demonstrating resolving powers up to 140. Similar solvent effects studies and applications have been reported by others [29,30].…”

Dopants and gas modifiers in ion mobility spectrometry

“…Information on dopants and modifiers applications in order to detect different analytes with DT-IMS and DMS are summarized in Table 3. sulfur hexafluoride, nitrogen oxides [80] acetone positive control of proton transfer CWA [47] gas modifiers for DT-IMS chiral modifiers: S-(+)-2-butanol R-(-)-2-butanol positive changing of collision cross-section for ions moving in drift section, analyte-modifier cluster formation stereoisomers [90] ketones, e.g., 5-nonanone positive analyte-modifier cluster formation separation of hydrazines and ammonia [38] ammonia positive analyte-modifier cluster formation separation of amine derivatives, and 2,4-lutidine [28] nitrobenzene positive analyte-modifier cluster formation separation of amine derivatives [92,93] ethyl lactate positive analyte-modifier cluster formation separation of atenolol, arginine, histidine, lysine, caffeine, and glucosamine [91,92] methanol positive analyte-modifier cluster formation separation of TTEA, asparagine, and valine [94] gas modifiers for DMS polar modiefiers, e.g., isopropanol, methanol, acetone positive negative clustering-declustering control many different compounds, increasing peak capacity [97][98][99][100] isopropanol, 1-butanol, ethyl acetate positive clustering-declustering control DNA damage markers [101] alcohols, acetone, acetonitrile, positive clustering-declustering control separation of drugs and metabolites [102] benzene (nonpolar modifier) positive - modifier-to-analyte interaction improvement in the sensitivity and selectivity of DMS for detection of aromatic compounds [106] …”

“…Detection of biomarkers of DNA damage was performed with DMS detector with isopropanol, 1-butanol and ethyl acetate gas modifiers [101]. It was shown that saturation effect is usually obtained at modifier concentration of about few % vol., but the dependence of peak position on modifier concentration varies for different pairs analyte-modifier.…”

Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

“…In particular, interactions with transport gases within the DMS instrument can have a substantial impact on ΔK. This can be used to great advantage, particularly for small molecules, where optimization of the transport gas by addition of volatile chemical modifiers can allow for high-resolution separation even of species with identical collision cross-sections [6][7][8][9]. On the other hand, these 'clustering' effects and others associated with the high field, high temperature environment within the DMS apparatus make quantitative determinations (of collision cross-section, for example) challenging even for relatively small molecules and effectively impossible for macromolecules.…”