Traditional separation and detection of targeted compounds from complex mixtures from environmental matrices requires the use of lengthy prefractionation steps and high-resolution mass analyzers due to the large number of chemical components and their large structural diversity (highly isomeric). In the present work, selected accumulation trapped ion mobility spectrometry (SA-TIMS) is coupled to Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for direct separation and characterization of targeted endocrine-disrupting compounds (EDC) from a complex environmental matrix in a single analysis. In particular, targeted identification based on high-resolution mobility (R ~ 70–120) and ultrahigh-resolution mass measurements (R > 400 000) of seven commonly targeted EDC and their isobars (e.g., bisphenol A, (Z)- and (E)-diethylstilbestrol, hexestrol, estrone, α-estradiol, and 17-ethynylestradiol) is shown from a complex mixture of water-soluble organic matter (e.g., Suwannee River Fulvic Acid Standard II) complemented with reference standard measurements and theoretical calculations (<3% error).

Thousands of chemically distinct compounds are encountered in fossil oil samples that require rapid screening and accurate identification. In the present paper, we show for the first time, the advantages of gas chromatography (GC) separation in combination with atmospheric-pressure laser ionization (APLI) and ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) for the screening of polyaromatic hydrocarbons (PAHs) in fossil oils. In particular, reference standards of organics in shale oil, petroleum crude oil, and heavy sweet crude oil were characterized by GC-APLI-FT-ICR MS and APLI-FT-ICR MS. Results showed that, while APLI increases the ionization efficiency of PAHs, when compared to other ionization sources, the complexity of the fossil oils reduces the probability of ionizing lower-concentration compounds during direct infusion. When gas chromatography precedes APLI-FT-ICR MS, an increase (more than 2-fold) in the ionization efficiency and an increase in the signal-to-noise ratio of lower-concentration fractions are observed, giving better molecular coverage in the m/z 100–450 range. That is, the use of GC prior to APLI-FT-ICR MS resulted in higher molecular coverage, higher sensitivity, and the ability to separate and characterize molecular isomers, while maintaining the ultrahigh resolution and mass accuracy of the FT-ICR MS separation.

In the present paper, we showed the advantages of trapped ion mobility spectrometry coupled too mass spectrometry (TIMS-MS) combined with theoretical calculations for fast identification (millisecond timescale) of polycyclic aromatic hydrocarbons (PAH) compounds from complex mixtures. Accurate PAH collision cross sections (CCS, in nitrogen as a bath gas) are reported for the most commonly encountered PAH compounds and the ability to separate PAH geometric isomers is shown for three isobaric pairs with mobility resolution exceeding 150 (3–5 times higher than conventional IMS devices). Theoretical candidate structures (optimized at the DFT/B3LYP level) are proposed for the most commonly encountered PAH compounds showing good agreement with the experimental CCS values (<5%). The potential of TIMS-MS for the separation and identification of PAH compounds from complex mixtures without the need of lengthy pre-separation steps is illustrated for the case of a complex soil mixture.

In the present paper, we describe the fundamentals and analytical advantages of Oversampling Selective Accumulation Trapped Ion Mobility Spectrometry (OSA-TIMS) when coupled to ultrahigh resolution mass analyzers (e.g., FT-ICR MS). During TIMS analysis, ion packages are spatially resolved based on their mobilities along the TIMS analyzer axis and multiple strategies can be utilized during the trapping and elution of the ion population of interest. In the case of OSA-TIMS-FT-ICR MS, the TIMS operation sequence, trapping conditions, and operations are optimized to increase the signal-to-noise and the number of points across the mobility domain, which leads to more accurate mobility and mass measurements. Experimental results show that accurate ion-neutral collision cross sections (<1%) can be measured using OSA-TIMS-FT-ICR MS with high mobility resolving powers (RIMS up to 250), high mass accuracy (<1 ppm), and ultrahigh mass resolution (RMS up to 600-1200k at m/z 400) in a single analysis. The analytical advantages of OSA-TIMS over SA-TIMS were illustrated for the analysis of structural peptide isomers (SDGRG and GRGDS [M + H](+)), conformational isomers (AT-hook peptide 3 KRGRGRPRK [M + 2H](+2)), and a complex mixture of polyaromatic hydrocarbons (PAH) from coal tar. Baseline separation of the structural peptide isomers SDGRG and GRGDS, [M + H](+), was observed, and three conformations were identified for the AT-hook peptide 3 KRGRGRPRK [M + 2H](+2) during OSA-TIMS-FT-ICR MS. A 2-fold increase in the number of molecular features and a 2-6-fold signal-to-noise increase was observed for OSA-TIMS when compared with SA-TIMS during the PAH analysis. This work provides the proof-of-principle for further application of OSA-TIMS-FT-ICR MS for the unsupervised analysis of complex mixtures based on the characterization of the conformational space and the assignment of chemical formulas in a single analysis.

In the present work, we demonstrate the potential and versatility of TIMS for the analysis of proteins, DNA-protein complexes and protein-protein complexes in their native and denatured states. In addition, we show that accurate CCS measurement are possible and in good agreement with previously reported CCS values using other IMS analyzers (<5% difference). The main challenges for the analysis of high mass proteins and protein complexes in the mobility and m/z domain are described. That is, the analysis of high molecular weight systems in their native state may require the use of higher electric fields or a compromise in the TIMS mobility resolution by reducing the bath gas velocity in order to effectively trap at lower electric fields. This is the first report of CCS measurements of high molecular weight biomolecules and biomolecular complexes (~ 150 kDa) using TIMS-MS.

In this work, nonlinear, stepping analytical mobility scan functions are implemented to increase the analytical separation and duty cycle during tandem Trapped Ion Mobility Spectrometry and FT-ICR MS operation. The differences between linear and stepping scan functions are described based on length of analysis, mobility scan rate, signal-to-noise, and mobility resolving power. Results showed that for the linear mobility scan function only a small fraction of the scan is sampled, resulting in the lowest duty cycle 0.5% and longest experiment times. Implementing nonlinear targeted scan functions for analysis of known mobilities resulted in increased duty cycle (0.85%) and resolving powers (R up to 300) with a 6-fold reduction in time from 30 to 5 min. For broad range characterization, a nonlinear mobility stepping scan function provided the best sensitivity, resolving power, duty cycle (4%), and points per peak. The applicability of nonlinear mobility scan functions for the analysis of complex mixtures is illustrated for the case of a direct infusion of a MCF-7 breast cancer cell digest, where isobaric peptides (e.g., DFTPAELR and TTILQSTGK) were separated in the mobility domain (R: 110) and identified based on their CCS, accurate mass (R: 550k), and tandem MS using IRMPD in the ICR cell.

For the first time, trapped ion mobility spectrometry (TIMS) in tandem with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is applied to the analysis of the low energy water accommodated fraction (WAF) of a crude oil as a function of the exposure to light. The TIMS-FT-ICR MS analysis provided, in addition to the heteroatom series identification, new insights into the WAF isomeric complexity (e.g., [m/z; chemical formula; collision cross section] datasets) for a better evaluation of the degree of chemical and structural photo-induced transformations. Inspection of the [m/z; chemical formula; collision cross section] datasets shows that the WAF composition changes as a function of the exposure to light in the first 115 hours by initial photo-solubilization of HC components and their photo-oxidation up to O4–5 of mainly high double bond equivalence species (DBE > 9). The addition of high resolution TIMS (resolving power of 90–220) to ultrahigh resolution FT-ICR MS (resolving power over 400k) permitted the identification of a larger number of molecular components in a single analysis (e.g., over 47k using TIM-MS compared to 12k by MS alone), with instances of over 6-fold increase in the number of molecular features per nominal mass due to the WAF isomeric complexity. This work represents a stepping stone towards a better understanding of the WAF components and highlights the need for better experimental and theoretical approaches to characterize the WAF structural diversity.

TIMS coupled to TOF MS and FT-ICR MS showed similar performance and high reproducibility. For the analysis of complex mixtures, both platforms were able to capture the major trends and characteristics; however, as the chemical complexity at the level of nominal mass increases with m/z (m/z >300-350), only TIMS-FT-ICR MS was able to report the lower abundance compositional trends.