Ion Mobility Spectrometry Mass Spectrometry

Ion mobility spectrometry (IMS) separates gas-phase ions drifting under an electric field according to their size
to charge ratio. We used electrospray ionization-drift tube IMS coupled to quadrupole mass spectrometry to obtain
the mobilities of common amino acids, amines, valinol, atenolol, and the chemical standards
tetramethylammonium ion (TMA), tetraethylammonium ion (TEA), tetrapropylammonium ion (TPA), and
tetrabutylammonium (TBA) ions, 2,4-lutidine and 2,6-di-tert-butyl pyridine (DTBP). The mobilities were
obtained in pure nitrogen or when shift reagents (SR) such as ammonia, 2-butanol, ethyl lactate, methanol, methyl
2-chloropropionate, nitrobenzene, 1-phenyl ethanol, trifluoromethyl benzyl alcohol, and water were introduced in
the buffer gas. We found important differences in the buffer gas temperature between different regions of the drift
tube and differences between the buffer gas and drift tube temperatures, which is normally used instead of the
buffer gas temperature in reduced mobility calculations. Therefore, we used the buffer gas temperature instead of
the drift tube temperature and a calibration method with two types of chemical standards, finding excellent
precision, reproducibilities from 0.3 to 0.6% for reduced mobilities (K0) of the chemical standards during nine
months. Repeatability during this period was 0.17% for the drift times of all the analytes. We also show that the
changes in instrumental parameters such as temperature, pressure and voltage that produce important variations
in drift times are small; for this, we recommend to calculate K0 from calibration with chemical standards instead
of replacing instrumental parameters in the IMS fundamental equations.

Calibration of the mobility scale in ion mobility spectrometry: the use of 2,4-lutidine as a chemical standard, the two-standard calibration method and the incorrect use of drift tube temperature for calibration † Roberto Fernández Maestre Ion mobility spectrometry (IMS) is an analytical technique that separates ions in the gas phase under the influence of an electric field according to their size to charge ratio. We used electrospray ionization IMS-quadrupole mass spectrometry to study the mobility shifts of 2,4-lutidine with temperature or the introduction of several contaminants in the drift gas. We found the reduced mobility (K 0) of 2,4-lutidine to decrease up to 24% when contaminants were introduced into the drift gas. We also show the significant variation of 2,4-lutidine's K 0 with the drift tube temperature, 8.5% from 100 to 322 C. These changes in 2,4-lutidine's mobility were due to variations in clustering by changes in temperature or contaminant concentration. This dependence of 2,4-lutidine's K 0 with temperature and contamination in the drift gas makes this chemical standard unsuitable to calibrate the mobility scale. Despite these findings, 2,4-lutidine is still used for this purpose. The shortcomings of the IMS two-standard calibration and the incorrect use of the drift tube temperature for calibration are also discussed. We suggest that accurate reduced mobilities must be determined for small ions only in a highly purified drift gas using calibrants with a well determined K 0 such as di tert-butyl pyridine at high temperatures, where clustering is low, and the drift gas temperature is measured instead of the drift tube temperature.

Gas chromatography mass spectrometry (GC-MS) was employed to determine the chemical composition of essential oil obtained from Eucalyptus globulus and Trachyspermum ammi. The essential oil obtained from leaves of Eucalyptus globulus and from seeds of Trachyspermum ammi by Clevenger apparatus. Chemical composition of the essential oils of E. globulus and T. ammi was analyzed by Gas chromatography – Mass spectrometry. Four main compounds in E. globulus were identified as Eucalyptol, Methyl –salicylate, Thymol, Para- cymene. 1, 8-cineole was found to be the main compound of E. globulus essential oil. Thymol, gamma- terpinene, para- cymene, beta- pinene were the main compounds of T. ammi oil and traces amount of beta myrcene, alpha- thujne, alpha- pinene, alpha- terpinene, carvacrol compounds of T. ammi were identified by GC-MS. Thymol was the main compound of T. ammi oil. The antifungal activity of E. globulus and T. ammi oils were screened against Trichophyton mentagrophytes and Epidermatophyton floccosum by using disc diffusion and modified micro dilution method. T. ammi oil shows highest inhibition zone in comparison to E. globulus oils and references antibiotics i.e. Clotrimazole and Ketoconazole.

The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early twentieth Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods and theory together with contributions from computational chemistry and gasphase ion chemistry which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS-mass spectrometry (IMS-MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi-/cross-disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilised for 'small molecule' species. This review focuses on the application of IMS-MS to 'small molecule' species typically used in drug discovery (from 100 to 500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods and applications are addressed. The typical application of IMS-MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (from 3-100) and the differences in collision cross-sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS-MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, 'small molecule' separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS-MS, not solely IMS, and small molecule applications.

We have studied the behavior of isomers and analogues by traveling wave ion mobility mass spectrometry (TWIM-MS) using
drift-gases with varying masses and polarizabilities. Despite the reduced length of the cell (18 cm), a pair of constitutional isomers, N-butylaniline and para-butylaniline, with theoretical collision cross-section values in helium (ΩHe) differing by as little  as 1.2 Å2 (1.5%) but possessing contrasting charge distribution, showed baseline peak-to-peak resolution (Rp-p) for their protonated molecules, using carbon dioxide (CO2), nitrous oxide (N2O) and ethene (C2H4) as the TWIM drift-gas. Near baseline Rp-p was also obtained in CO2 for a group of protonated haloanilines (para-chloroaniline, para-bromoaniline and para-iodoaniline) which display contrasting masses and theoretical ΩHe, which differ by as much as 15.7Å2 (19.5%) but similar charge distributions. The deprotonated isomeric pair of trans-oleic acid and cis-oleic acid possessing nearly identical theoretical ΩHe and ΩN2 as well as similar charge distributions, remained unresolved. Interestingly, an inversion of drift-times were observed for the 1,3-dialkylimidazolium ions when comparing He, N2 and N2O. Using density functional theory as a means of examining the ions electronic structure, and He and N2-based trajectory method algorithm, we discuss the effect of the long-range charge induced dipole attractive and short-range Van der Waals forces involved in the TWIM separation in drift-gases of differing polarizabilities. We therefore propose that examining the electronic structure of the ions under investigation may potentially indicate whether the use of more polarizable drift-gases could improve separation and the overall success of TWIM-MS analysis.

Heparin interacts with many proteins and is involved in biological processes such as anticoagulation, angiogenesis, and antitumorigenic activities. These heparin-protein interactions can be influenced by the binding of various metal ions to these complexes. In particular, physiologically relevant metal cations influence heparin-protein conformations through electronic interactions inherent to this polyanion. In this study, we employed ion mobility mass spectrometry (IMMS) to observe conformational changes that occur in fully-sulfated heparin octasaccharides after the successive addition of metal ions. Our results indicate that binding of positive counter ions causes a decrease in collision cross section (CCS) measurements, thus promoting a more compact octasaccharide structure.

The combination of liquid chromatography and mass spectrometry (LC-MS) is a powerful and indispensable analytical tool that is widely applied in many areas of chemistry, medicine, pharmaceutics and biochemistry. In this review recent MS instrumental developments are presented as part of a special issue covering various aspects of liquid chromatography tandem mass spectrometry (LC-MS/MS) in clinical chemistry. Improvements, new inventions as well as new combinations in ion source technology are described focusing on dual or multimode sources and atmospheric pressure photoionization (APPI). Increasing demands regarding sensitivity, accuracy, resolution and both quantitation and identification guarantee ongoing improvements in mass analyzer technology. This paper discusses new hybrid MS instruments that can perform novel scan modes as well as high-resolution mass spectrometers (HRMS) that finally seem to be able to overcome, or at least significantly reduce, their weaknesses in quantitative applications. Ion mobility-mass spectrometry (IMMS) itself is not an invention of the last 10 years, but a lot of progress was made within the last decade that reveals the potential benefits of this combination. This is clearly reflected by the increased number of commercially available instruments and the various designs of IMMS are covered in detail in this review. Selected applications for all these instrumental developments are given focusing on the perspective of clinical chemistry.

Ion mobility spectrometry (IMS) is an analytical technique that separates gas-phase ions drifting under an electric field according to their size to charge ratio. We used electrospray ionization-drift tube IMS coupled to quadrupole mass spectrometry to measure the mobilities of glucosamine (GH +) and caffeine (CH +) ions in pure nitrogen or when the shift reagent (SR) 2-butanol was introduced in the drift gas at 6.9 mmol m-3. Binding energies of 2-butanol-ion adducts were calculated using Gaussian 09 at the CAMB3LYP/6-311++G(d,p) level of theory. The mobility shifts with the introduction of 2-butanol in the drift gas were-2.4% (GH +) and-1.7% (CH +) and were due to clustering of GH + and CH + with 2-butanol. The formation of GBH + was favored over that of CBH + because GBH + formed more stable hydrogen bonds (83.3 kJ/mol) than CBH + (81.7 kJ/mol) for the reason that the positive charge on CH + is less sterically available than on GH + and the charge is stabilized by resonance in CH +. These results are a confirmation of the arguments used to explain the drift behavior of these ions when ethyl lactate SR was used (Bull Kor Chem Soc 2014, 1023-1028). This study is a step forward to predict IMS separations of overlapping peaks in IMS spectra, simplifying a procedure that is trial and error by now.

Expression of the protruding (P) domain of the norovirus capsid protein, in vitro, results in the formation of P dimers and larger oligomers, 12-mer and 24-mer P particles. All these P complexes retain the authentic antigenicity and carbohydrate-binding function of the norovirus capsid. They have been used as tools to study norovirus-host interactions, and the 24-mer P particle has been proposed as a vaccine and vaccine platform against norovirus and other pathogens.

Matrix-assisted laser desorption/ionization (MALDI) coupled with ion mobility-mass spectrometry (IM-MS) provides a rapid (s-ms) means for the two-dimensional (2D) separation of complex biological samples (e.g., peptides, oligonucleotides, glycoconjugates, lipids, etc.), elucidation of solvent-free secondary structural elements (e.g., helices, ␤-hairpins, random coils, etc.), rapid identification of posttranslational modifications (e.g., phosphorylation, glycosylation, etc.) or ligation of small molecules, and simultaneous and comprehensive sequencing information of biopolymers. In IM-MS, protein-identification information is complemented by structural characterization data, which is difficult to obtain using conventional proteomic techniques. New avenues for enhancing the figures of merit (e.g., sensitivity, limits of detection, dynamic range, and analyte selectivity) and optimizing IM-MS experimental parameters are described in the context of deriving new information at the forefront of proteomics research.

α-Trifluoromethyl benzyl alcohol (F)& was introduced as a “shift reagent” in the buffer gas of an electrospray ionization ion mobility spectrometer coupled to a quadrupole mass spectrometer to explain the mobility shifts of selected compounds; ion mobilities depended on ion sizes and F-ion adducts binding energies calculated using Gaussian 09 at the X3LYP/6-311++G(d,p) level. The mobility shifts with the introduction of F in the buffer gas were: -13% (ethanolamine), -10.6% (serine), -8.6% (threonine), -7.3% (phenylalanine), -7.0% (tyrosine), -6.2 (tributylamine), -5.1% (valinol), -4.7% (methionine), -3.9% (tryptophan), -3.1% (tribenzylamine), -1.3% (2,6-di-tert-butyl pyridine, DTBP), -1.2% (2,4-lutidine, 2,4-dimethyl pyridine), -0.1% (atenolol). These mobility shifts showed a decreasing trend with the increase in molecular weight from ethanolamine to tribenzylamine excluding some ions due to steric hindrance (2,4-lutidine, DTBP and tetraalkylammonium ions), formation of intramolecular bridges (atenolol and methionine) or low binding energy with F (valinol). Ethanolamine (61.1 g/mol) showed the largest mobility shift (-13%) due to its low molecular weight and tribenzylamine showed the smallest one due to its large size. We found a similar trend in mobility shifts when methyl chloro propionate, trifluoromethyl benzyl alcohol, ethyl lactate, nitrobenzene or 2-butanol were used as SR. We also found that penicillamine adducts with F were not seen in the mass or mobility spectra probably because of the formation of an intramolecular bridge in this compound; F produced the average lowest mobility shifts of all SR tried before, even of smaller size, (methyl chloro propionate, phenylethanol, ethyl lactate, nitrobenzene, and 2-butanol) because of the inductive effects exerted by the three fluorine atoms that decreased F proton affinity and hindered its adduction to analyte ions. In summary, intramolecular bridges, size, inductive effects, steric hindrance and adduct binding energy were used to explain mobility shifts when trifluoromethyl benzyl alcohol was used as a “shift reagent” in ion mobility spectrometry.

The mobilities of a set of common α-amino acids, four tetraalkylammonium ions, 2,4-dimethyl pyridine (2,4-lutidine), 2,6-di-tert-butyl pyridine (DTBP), and valinol were determined using electrospray ionization-ion mobility spectrometry-quadrupole mass spectrometry (ESI-IMS-QMS) while introducing 2-butanol into the buffer gas. The mobilities of the test compounds decreased by varying extents with 2-butanol concentration in the mobility spectrometer. When the concentration of 2-butanol increased from 0.0 to 6.8 mmol m(-3) (2.5×10(2) ppmv), percentage reductions in mobilities were: 13.6% (serine), 12.2% (threonine), 10.4% (methionine), 10.3% (tyrosine), 9.8% (valinol), 9.2% (phenylalanine), 7.8% (tryptophan), 5.6% (2,4-lutidine), 2.2% (DTBP), 1.0% (tetramethylammonium ion, TMA, and tetraethylammonium ion, TEA), 0.0% (tetrapropylammonium ion, TPA), and 0.3% (tetrabutylammonium ion, TBA). These variations in mobility depended on the size and steric hindrance on the charge of the ions, and were due to formation of large ion-2-butanol clusters. This selective variation in mobilities was applied to the resolution of a mixture of compounds with similar reduced mobilities such as serine and valinol, which overlapped in N(2)-only buffer gas in the IMS spectrum. The relative insensitivity of tetraalkylammonium ions and DTBP to the introduction of 2-butanol into the buffer gas was explained by steric hindrance of the four alkyl substituents in tetraalkylammonium ions and the two tert-butyl groups in DTBP, which shielded the positive charge of the ion from the attachment of 2-butanol molecules. Low buffer gas temperatures (100 °C) produced the largest reductions in mobilities by increasing ion-2-butanol interactions and formation of clusters; high temperatures (250 °C) prevented the formation of clusters, and no reduction in ion mobility was obtained with the introduction of 2-butanol into the buffer gas. Low temperatures and high concentrations of 2-butanol produced a series of ion clusters with one to three 2-butanol molecules in compounds without steric hindrance. Clusters of two and three molecules of 2-butanol were also visible. Ligand-saturation on the positive ions with 2-butanol molecules occurred at high concentrations of modifier (6.8 mmol m(-3) at 150°C); when saturated, no further reduction in mobility occurred when 2-butanol was introduced into the buffer gas.

Aim: Demonstrate that from the numerous methods of detecting explosive materials, ion-mobility spectrometry can be one of the most effective approaches for use in laboratory and field conditions.

Methodology: During research performed and recorded ion mobility spectra (drift time spectrum) with the aid of a spectrometer and conducted an effectiveness analysis of explosive material identification based on a series of performed measurements.

Results: A critical analysis of contemporary techniques for detecting explosive materials included: electrochemical methods, chemiluminescent, optical, optoelectronic, biochemical and methods based on terahertz imaging. Special attention was devoted to ion mobility spectrometry (IMS) and to the testing of effectiveness of the IMS analytical technique in the detection of explosive materials.

Conclusions: Threats associated with the potential use of explosives by groups endangering public security e.g. terrorist organizations, culminate in a search for effective ways to counteract such hazards. A solution may lie in a broad application of techniques, which facilitate quick detection of explosive materials in public areas. The task is not straightforward because in practice one may encounter the use of numerous materials and detonation systems, including Improvised Explosive Devices (IED). The explosives used may come from various sources. Apart from traditional explosives, materials used in mining as well as mixtures of generally available chemical substances may be used. Analytical chemistry techniques, for use in the detection of explosive materials are effective, mainly in laboratory conditions, because, in essence, the techniques make use of stationery measuring equipment. Ion Mobility Spectrometry is the most universal method. Because of its characteristics; chemical ionisation under atmospheric pressure and simplification of construction, provides a potential for application in diverse conditions.