High-resolution Ion Mobility Mass Research Articles

An experimental investigation into the reduced mobilities of lanthanide cations using high-resolution ion mobility mass spectrometry

Reduced mobilities for ground-state electronic configurations of the complete lanthanide series of cations, excluding promethium, have been measured. These values were obtained using an ion mobility mass spectrometer that utilizes a 2m drift tube to generate high-resolution ion mobility data. In all cases, lanthanide cations were generated using pulsed-laser vaporization of either a metal rod or foil target. The mobilities of Eu+, Gd+, Yb+, and Lu+ have been previously examined and these data are also included. All other lanthanide cation mobilities, measured in He, are reported here for the first time. A discussion of the observed trends in the mobilities of the lanthanide series is also provided.

Practical application of in silico fragmentation based residue screening with ion mobility high-resolution mass spectrometry.

A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high-resolution mass spectrometry LC/IMS-HRMS is presented. The comprehensive four-dimensional data (chromatographic retention time, drift time, mass-to-charge and ion abundance) obtained in data-independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. The utilized data-independent acquisition mode relies on the MSE concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances). Copyright © 2017 John Wiley & Sons, Ltd.

Prediction of Collision Cross-Section Values for Small Molecules: Application to Pesticide Residue Analysis.

The use of collision cross-section (CCS) values obtained by ion mobility high-resolution mass spectrometry has added a third dimension (alongside retention time and exact mass) to aid in the identification of compounds. However, its utility is limited by the number of experimental CCS values currently available. This work demonstrates the potential of artificial neural networks (ANNs) for the prediction of CCS values of pesticides. The predictor, based on eight software-chosen molecular descriptors, was optimized using CCS values of 205 small molecules and validated using a set of 131 pesticides. The relative error was within 6% for 95% of all CCS values for protonated molecules, resulting in a median relative error less than 2%. In order to demonstrate the potential of CCS prediction, the strategy was applied to spinach samples. It notably improved the confidence in the tentative identification of suspect and nontarget pesticides.

A Powerful Four-Dimensional Separation Method for Complex Samples

A two-dimensional LC (2D-LC) method was coupled to an ion mobility–high-resolution mass spectrometer (IM–MS), which enables the separation of complex samples in four dimensions [2D-LC, ion mobility (IM) and mass spectrometry (MS)]. This approach works as a continuous multiheart-cutting LC-system, using a long modulation time of four minutes, in comparison to comprehensive two-dimensional liquid chromatography, which allows the complete transfer of most of the first dimension peaks to the second dimension column without fractionation. Hence, each compound delivers only one peak in the second dimension, which simplifies the data handling even when ion mobility as a third and mass spectrometry as a fourth dimension are introduced. The analysis of different complex samples, such as a plant extract from Hediotys diffusa and Scutellaria barbata, a waste water inflow, and a biocoal sample, was shown. The results of the four-dimensional separation method demonstrate that with the same column combination and the same solvents and gradients, that means without method optimization, totally different samples can be separated with outstanding separation power. Each sample was spiked with cyclophosphamide and ifosfamide and the ion suppression was determined by comparison of the peak area in the complex samples and in pure water after analysis of these samples with a 1D-LC and a 2D-LC approach. It is shown that the 2D-LC method allows an external calibration for the spiked compounds in the plant and waste water sample because of the higher separation power in comparison with 1D-LC.

Reduced mobilities of lanthanide cations measured using high-resolution ion mobility mass spectrometry with comparisons between experiment and theory

Reduced mobilities for ground-state electronic configurations of Eu+, Gd+, Yb+, and Lu+ have been measured using a high-resolution ion mobility mass spectrometer. The instrument uses a 2m drift tube to generate high-resolution ion mobility data. Lanthanide cations were generated using pulsed-laser vaporization of either a metal rod or foil target. The mobilities of these four lanthanide cations have been previously studied using high-quality ab initio calculations, to determine potential energy curves that described their interactions with the noble gases (He to Xe). A comparison between experimental and theoretical results shows extremely good agreement in three of the four systems.

New High Resolution Ion Mobility Mass Spectrometer Capable of Measurements of Collision Cross Sections from 150 to 520 K.

We present a new variable temperature (VT), high resolution ion mobility (IM) drift tube coupled to a commercial mass spectrometer (MS). Ions are generated in an electrospray ion source with a sampling cone interface and two stacked ring RF guides which transfer ions into the mobility analyzer located prior to a quadrupole time-of-flight mass spectrometer. The drift cell can be operated over a pressure range of 0.5-3 Torr and a temperature range of 150-520 K with applied fields typically between 3 and 14 V cm-1. This makes the instrument suitable for rotationally averaged collision cross section (CCS) measurements at low E/N ratios where ions are near thermal equilibrium with the buffer gas. Fundamental studies of the effective ion temperatures can be performed at high E/N ratios. An RF ion trap/buncher is located at the beginning of the drift region, which modulates the continuous ion beam into spatially narrow packets. Packets of ions then drift in a linear electric field, which is 50.5 cm long, and are separated according to their mobility in an inert buffer gas. Post-drift, an ion funnel focuses the radially spread pulses of ions into the inlet of a commercial MS platform (Micromass QToF2). We present the novel features of this instrument and results from VT-IM-MS experiments on a range of model systems-IMS CCS standards (Agilent ESI Tune Mix), the monomeric protein Ubiquitin (8.6 kDa), and the tetrameric protein complex Concanavalin A (103 kDa). We evaluate the performance of the instrument by comparing ambient DTCCSHe values of model compounds with those found in the literature. Several effects of temperature on collision cross sections and resolution are observed. For small rigid molecules, changes in resolution are consistent with anticipated thermal diffusion effects. Changes in measured DTCCSHe for these rigid systems at different temperatures are attributed primarily to the effect of temperature on the long-range attractive interaction. Similar effects are seen for protein ions at low temperatures, although there is also some evidence for structural transitions. By heating the protein ions, their conformational profiles are significantly altered. Very high temperatures narrow the conformational space presented by both Ubiquitin and Concanavalin; it appears that diverse conformational families are "melted" into more homogeneous populations. Because of this conformational heterogeneity, the apparent IMS resolution obtained for proteins at ambient and reduced temperatures is an order of magnitude lower than the expected diffusion limited resolution (Rmax). This supports a hypothesis that the broad DTCCSHe features frequently observed for proteins do not correspond to interconverting conformers, but rather to high numbers of intrinsically stable structures.

Characterizing the electronic states of the second-row transition metal cations using high-resolution ion mobility mass spectrometry

Reduced mobilities for ground-state and electronic excited-state configurations of the second-row transition metal cations, excluding Tc+, have been measured. These values were obtained using an ion mobility mass spectrometer that utilizes a 2m drift tube to generate high-resolution ion mobility data. Several of these atomic cations have been previously studied and the results obtained here are compared to reduced mobilities reported in the literature. In all cases, ions were generated using pulsed-laser vaporization of either a metal rod or foil target. Presented here for the first time are the reduced mobilities of Y+, Ru+, and Rh+. A discussion of the observed trends in the mobilities of the second-row transition metal series, relative to those measured for the first-row series, is also provided.

Metabolic profiling of human blood by high-resolution ion mobility mass spectrometry (IM-MS)

A high-resolution ion mobility time-of-flight mass spectrometer with electrospray ionization source (ESI-IM-MS) was evaluated as an analytical method for rapid analysis of complex biological samples such as human blood metabolome. The hybrid instrument (IM-MS) provided an average ion mobility resolving power of ∼90 and a mass resolution of ∼1500 (at m/ z 100). A few μL of whole blood was extracted with methanol, centrifuged and infused into the IM-MS via an electrospray ionization source. Upon IM-MS profiling of the human blood metabolome approximately 1100 metabolite ions were detected and 300 isomeric metabolites separated in short analyses time (30 min). Estimated concentration of the metabolites ranged from the low micromolar to the low nanomolar level. Various classes of metabolites (amino acids, organic acids, fatty acids, carbohydrates, purines and pyrimidines, etc.) were found to form characteristic mobility-mass correlation curves (MMCCs) that aided in metabolite identification. Peaks corresponding to various sterol derivatives, estrogen derivatives, phosphocholines, prostaglandins, and cholesterol derivatives detected in the blood extract were found to occupy characteristic two-dimensional IM-MS space. Low abundance metabolite peaks that can be lost in MS random noise were resolved from noise peaks by differentiation in mobility space. In addition, the peak capacity of MS increased sixfold by coupling IMS prior to MS analysis.