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Background: Identification and characterization of steroids from complex mixtures with isomeric precision is key to studying endocrine-related metabolism and disorders. Whereas the golden standard chromatography, including liquid chromatography and gas chromatography, can be coupled with mass spectrometry to separate steroids prior to ionization, this separation is time-consuming. Contrarily, direct infusion techniques can offer increased throughput; however, these are often hampered by limited structural specificity. Thus, it is important to develop new analytical tools for direct infusion mass spectrometry that will provide isomeric specificity. Results: Herein, we show that direct infusion with electrospray ionization in combination with silver adduction and cyclic ion mobility mass spectrometry (cIMS) enables mobility separation and improves the detectability of steroid isomers. Specifically, silver ion adduction of steroids increases instrumental response up to 14 times and enables almost baseline mobility separation of closely related structural steroid isomers even at low cIMS resolution. By combining experimental and theoretical data, we show that the silver interacts with the steroid isomer at single or multiple sites, which introduces conformational changes that enable mobility separation. Moreover, we show that the combination of cIMS and silver adduct fragmentation in tandem mass spectrometry provides an additional dimension for annotation of steroid isomers. Thus, the simple introduction of silver ions into the electrospray solvent provides a great gain in the analytical discernment of steroid isomers. Significance: For the first time, we show that the use of silver adduction introduces a conformational change in steroids that allows for them to be separated with low-resolution ion mobility spectrometry without any prior derivatization, chromatographic separation, or instrumental modification. This is a new and important tool for analyzing steroid isomers that can unravel their importance in biological systems.

The quantification of the effects of space radiation for manned spaceflight can be approximated by nanodosimetric measurements. For the development of nanodosimetric detectors, a Monte Carlo model for ion mobility and diffusion for characteristic electric fields is presented.This model can be used to describe the interactions of ions in their parent gas based solely on commonly known input parameters, such as the ionization potential, kinetic diameter, molar mass, and polarizability of the gas. A model for approximating the resonant charge exchange cross section has been proposed, requiring only the ionization energy and mass of the parent gas as input parameters. The method proposed in this work was tested against experimental drift velocity data for a wide range of gases (helium, neon, nitrogen, argon, krypton, carbon monoxide, carbon dioxide, oxygen, propane). The transverse diffusion coefficients were compared to experimental values for helium, nitrogen, neon, argon, and propane gas.With the Monte Carlo code and resonant charge exchange cross section approximation model presented in this work, it is now possible to calculate an estimate of the drift velocities, transverse diffusion, and thus the ion mobility of ions in their parent gas. This is essential for further nanodosimetric detector development, as those parameters are often not well known for the gas mixtures used in nanodosimetry.

Mass spectrometry is one of the most extensive scientific analysis techniques, which plays an important role in analysis and research of biology, pharmaceutical, chemical industry, new materials and so on. At present, the research method of organic reaction mechanism is mainly through the detection of hypothetical organic reaction intermediates, combined with density functional calculation. Therefore, it is of great significance for mass spectrometer with high sensitivity to analyze and detect the intermediates in organic reactions. In this study, C-C coupling reaction in Suzuki-Miyaura reaction was studied. 3-Bromopyridine, 3-bromoquinoline and 3-bromo-5-phenylpyridine were used to react with phenylboronic acid, 2-methylphenylboric acid and 3,5-dimethylphenylboric acid, respectively, and Pd(PPh3)4 was used as catalyst to carry out one-pot reaction in toluene solvent. During the reaction, the samples were taken at regular intervals, and the intermediates generated after the oxidative addition and transmetalation processes in the Suzuki-Miyaura coupling reaction were detected using electrospray ionization-ion mobility time-of-flight mass spectrometry (ESI-TIMS-TOF MS). The results showed that:1) For the intermediates formed in the oxidative addition process, arylboric acids are not involved in the formation of arylboric acids, the mass-charge ratios observed in the reactions with different arylboric acids are the same. While, the intermediates formed after transfer metallization are different with the two substances involved in the coupling reaction. 2) The isotopic peaks of the detected intermediates are consistent with the predicted spectra. 3) The ion mobility of the detected groups can be detected by TIMS-TOF to distinguish the isomers, and the fragmented small groups can be observed by MS/MS analysis of the detected intermediates. The data of mass-charge ratio, ion mobility and MS/MS obtained by TIMS-TOF are helpful to study organic reaction mechanism, and also can provide a reference for the reaction mechanism catalyzed by metal Pd.

Introduction: Steroid measurements are important for diagnosis and monitoring of many conditions and treatment regiments; however, due to structural and chemical similarities amongst steroids, these analyses are challenging, even for highly specific techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential mobility spectrometry (DMS) has the potential to improve these analyses by providing an orthogonal and complementary separation technique. Methods: Initially, the potential for DMS to improve signal-to-noise ratio (S/N) and reduce interference was tested by comparing chromatograms acquired with and without DMS when performing measurements of six different steroids. Subsequently, a full clinical validation of cortisol and cortisone in urine was performed with the LC-DMS-MS/MS method. Results and Discussion: DMS significantly reduced interferences observed in the chromatograms and boosted S/N by between 1.6 and 13.8 times. Additionally, DMS improved the agreement between quantifier/qualifier fragment ion results for cortisol and cortisone as indicated by the increase in R2 from approximately 0.81 to 0.98. All validation studies met acceptance criteria and we observed exceptional analytical performance in terms of precision, with % CVs less than 8%. Conclusions: DMS improved the specificity of the steroid measurements by reducing interferences and improving S/N. The validation studies prove that these benefits did not come at the expense of other aspects of analytical performance. This study indicates that DMS has the potential to benefit not just clinical measurements of challenging analytes, but many clinical LC-MS/MS analyses.

Ion transport plays an important role in various biological processes because of the ability of ions to move rapidly in biological ion channel‐confined spaces. For example, rapid proton transport in ATPases is attributed to confined channel spaces and conjugated sites. According to molecular dynamics simulations, the confined spaces and conjugated sites in nanochannels can enhance ion transport. Herein, it is demonstrated that the ATPase‐like structures of sulfonic acid‐modified covalent organic framework nanochannels, which promote the formation of highly ordered and continuous water molecular chains and confined spaces, can support ion (H+, Li+, Na+, and K+) transport rates that are an order of magnitude higher than those of bulk water. The ion transport rates in the nanochannel are superior to those in other artificial channels. Moreover, the selectivity of cations in the nanochannel is evaluated using the diffusion potential with a concentration gradient. The simulations and experimental results demonstrate that confined spaces and conjugated sites are crucial for efficient ion transport in nanochannels modified by sulfonic acid groups as cation conductor materials.

Nearly all the life activities are regulated by the interactions of the protein with other biomolecules, including protein-protein interactions (PPIs) and protein-ligand interactions (PLIs), therefore understanding interaction and structural characterization of formed complexes represent a key task for modern bioscience. Conventional biophysical techniques like circular dichroism spectroscopy (CD), fluorescence resonance energy transfer (FRET), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC), are limited in studying protein complexes structures and interactions, considering sample purity is a major issue for obtaining reliable data with conventional methods mentioned above. Additional technologies are required to complement structural biology and interactomics research, while mass spectrometry (MS) can deal with impurities or even mixtures in principle, therefore native mass spectrometry (nMS) is demonstrated as a powerful tool to bridge the gap between structural biology and interactomics research. As the most widespread soft ionization technique, electrospray ionization is utilized in native mass spectrometry, which employs volatile aqueous solution, near physiological pH and gentle desolvation conditions to make the transfer of weakly bound noncovalent complexes into the gas phase while preserving their integrity and native structure possible. In this way, stoichiometry, binding partners, thermodynamics, structural dynamics, and topology information on transferred noncovalent complexes can be acquired. A recent breakthrough in native MS sample preparation demonstrated direct analysis of overexpressed proteins from crude cell lysates, which significantly simplified sample purification procedures. Innovations in mass spectrometry instruments, such as extended m/z range quadrupole stages or modification of Orbitrap instruments allow access to high mass with little compromise in resolving power. This has promoted the native analysis of protein complexes and diverse protein interaction networks to elucidate their architecture, as well as enabled the identification of small differences in proteoforms. While coupling with either ion mobility spectrometry (IMS) or capillary electrophoresis (CE), the analytical ability of native MS can be greatly extended. In this review, the technologies in native mass spectrometry and several cases in recent reports from five aspects were introduced, such as sample preparation, ion source, instrumentation, ion mobility mass spectrometry and coupling with capillary electrophoresis, challenges for the future development of native mass spectrometry.

Ion mobility coupling with mass spectrometer has become an important tool for analysis of complex mixtures. Generally, the type and composition of drift gas (e.g., N2, He, CO2) in an ion mobility spectrometer will impact on the separation of different types of analytes and transmission of ions with a wide mass range. U-shaped mobility analyzer (UMA) is a unique type of mobility device based on counter-flow mobility principle, and it can sort specific types of ions with high mobility resolving power under the co-effect of electric field and gas flow. UMA has independent drift gas channels which allows the drift gas in and out with high speed and accurate control, hence the on-line adjustment of the gas composition becomes possible. The effects of changing drift gas composition on sensitivity, separation capability and analysis speed were examined in this study. From the preliminary results, when using a mixture of drift gas, the mobility peak position (drift field strength) linearly correlated with the gas composition and met the predication of the Blanc′s law. With the constant drift gas velocity, the mobility resolution from He is lower than those from the heavier drift gas (N2 or CO2) based on our theory, but the ion transmission is much higher (better RF confinement in He) and the separation time can also be reduced. On the other hand, if keeping the peak position constant (adjusting drift gas velocity for different gas), the resolution from He can even theoretically surpass that from N2 or CO2 with the expense of sensitivity reduction. Therefore, optimum and balanced results for different applications (e. g. better separation for isomer analysis in N2 or CO2 with doping a specific ratio of He, fast and high sensitivity data acquisition for DDA or DIA operation in pure He) can be achieved by adjusting the drift gas composition. Finally, the possibility and advantages of dynamically controlling the gas composition were discussed, which may provide new perspectives for coupling with LC separation of very complex samples.

Identification and determination of chiral pharmaceutical residues is still a challenging analytical puzzle. In this work, a simple, rapid, and effective method for chiral D/L-tetraiodothyronine (T4) separation and quantitative was developed based on host–guest recognition using ion mobility spectrometry-mass spectrometry (IMS-MS). The D/L-T4 enantiomers were mobility separated by their diastereomeric complexes through mixing with cyclodextrin (CD) and metal ions. D/L-T4 was first separated by complexing with host molecule (α-, β-, γ-CD), observing weak peak-to-peak resolution (Rp-p) by the formed binary complex [CD + D/L-T4-H]+, and the Rp-p decreased with the CD size increasing. However, the separation effect of D/L-T4 was much improved with the addition of divalent metal ions (G2+) by the formed ternary complex [CD + D/L-T4 + G]2+. In comparison, α-CD related complexes can possess the best separation effect for D/L-T4 in most cases. Considering the high selectivity, non-toxic, and chemically stable of β-CD, [β-CD + D/L-T4 + Ca]2+ was selected for D/L-T4 analysis (RP-P = 0.764). Whereafter, chemical theoretical conformations for [β-CD + D/L-T4 + H]+ and [β-CD + D/L-T4 + Ca]2+ were optimized, discovering similar micro-interaction modes between [β-CD + D-T4 + H]+ and [β-CD + L-T4 + H]+; while with the addition of Ca2+, significantly different interaction modes were observed between [β-CD + D-T4 + Ca]2+ and [β-CD + L-T4 + Ca]2+. And theoretical collision cross section (CCS) trends for the complexes were consistent with that of the experimental results. Additionally, calibration curves were linear within 1.00 to 104 ng mL−1 with coefficient (R2 > 0.99), gaining the limit of detection (LODs) calculation of 0.11 ng mL−1, and the detection range between D-T4 and L-T4 of 45.6:1 to 1:59.8. Finally, the method was applied for D/L-T4 detection in Levothyroxine tablets, the detection content has good consistency on drug labeling. Because the proposed method exhibited good analytical performance in terms of speed, selectivity, sensitivity, and reproducibility of the measurements, that can be a promising strategy for effective D/L-T4 detection in pharmaceutical industries or other practical samples.

Drug resistance remains one of the main causes of poor outcome in cancer therapy. It is also becoming evident that drug resistance to both chemotherapy and to antibiotics is driven by more than one mechanism. So far, there are at least eight recognized mechanisms behind such resistance. In this review, we choose to discuss one of these mechanisms, which is known to be partially driven by a class of transmembrane proteins known as ATP-binding cassette (ABC) transporters. In normal tissues, ABC transporters protect the cells from the toxic effects of xenobiotics, whereas in tumor cells, they reduce the intracellular concentrations of anticancer drugs, which ultimately leads to the emergence of multidrug resistance (MDR). A deeper understanding of the structures and the biology of these proteins is central to current efforts to circumvent resistance to both chemotherapy, targeted therapy, and antibiotics. Understanding the biology and the function of these proteins requires detailed structural and conformational information for this class of membrane proteins. For many years, such structural information has been mainly provided by X-ray crystallography and cryo-electron microscopy. More recently, mass spectrometry-based methods assumed an important role in the area of structural and conformational characterization of this class of proteins. The contribution of this technique to structural biology has been enhanced by its combination with liquid chromatography and ion mobility, as well as more refined labelling protocols and the use of more efficient fragmentation methods, which allow the detection and localization of labile post-translational modifications. In this review, we discuss the contribution of mass spectrometry to efforts to characterize some members of the ATP-binding cassette (ABC) proteins and why such a contribution is relevant to efforts to clarify the link between the overexpression of these proteins and the most widespread mechanism of chemoresistance.

Accelerated storage is routinely used with pharmaceuticals to predict stability and degradation patterns over time. The aim of this is to assess the shelf life and quality under harsher conditions, providing crucial insights into their long-term stability and potential storage issues. This study explores the potential of transferring this approach to food matrices for shelf-life estimation. Therefore, hazelnuts were stored under accelerated short-term and realistic long-term conditions. Subsequently, they were analyzed with high resolution mass spectrometry, focusing on the lipid profile. LC-MS analysis has shown that many unique processes take place under accelerated conditions that do not occur or occur much more slowly under realistic conditions. This mainly involved the degradation of membrane lipids such as phospholipids, ceramides, and digalactosyldiacylglycerides, while oxidation processes occurred at different rates in both conditions. It can be concluded that a food matrix is far too complex and heterogeneous compared to pharmaceuticals, so that many more processes take place during accelerated storage, which is why the results cannot be used to predict molecular changes in hazelnuts stored under realistic conditions.

Abstract To make accurate measurements, field mills must be calibrated in a known DC electric field space charge in which the quantities can be control1ed. A simulation model of the generation apparatus of the electric field with a space charge has been built. Based on the combination of the electric field and the transfer of a dilute substances model, the influence of openings in the metal screen was calculated. Simulation results showed that the opening size of the high‐voltage electrode has a great influence on the distribution of the electric field and ion density at the calibration zone. Next, a generation apparatus was designed and developed and ion mobility was researched. The experimental results showed that ion mobility decreased with an increase in electric field strength. However, ion mobility tends to be saturated when the electric field reaches a certain critical value. Two fitting formulas of ion mobility of positive and negative charge are proposed that can be used to predicate ion mobility in a high electric field.

Ion transport properties in metal halide perovskite still constitute a subject of intense research because of the evident connection between mobile defects and device performance and operation degradation. In the case of X‐ray detectors, dark current level and instability are regarded to be connected to the ion migration upon bias application. Two compositions (MAPbBr3 and MAPbI3) and structures (single‐ and microcrystalline) are checked by the analysis of long‐term dark current evolution. Electronic current increases with time before reaching a steady‐state value within a response time (from 104 down to 10 s) that strongly depends on the applied bias. A coupling between electronic transport and ion kinetics exists that ultimately establishes the time scale of electronic current. Effective ion mobility μi is extracted for a range of applied electric field ξ. While ion mobility results field‐independent in the case of MAPbI3, a clear field enhancement is observed for MAPbBr3 (∂μi/∂ξ>0), irrespective of the crystallinity. Both perovskite compounds present effective ion mobility in the range of μi ≈ 10−7–10−6 cm−2 V−1 s−1, in accordance with previous analyses. The ξ‐dependence of the ion mobility is related to the lower ionic concentration of the bromide compound. Slower migrating defect drift is suppressed in the case of MAPbBr3, in opposition to that observed here for MAPbI3.

Salinity gradient energy has gained attention in recent years as a renewable energy source, especially employing reverse electrodialysis technology (RED), which is based on the role of ion exchange membranes. In this context, many efforts have been developed by researchers from all over the world to advance the knowledge of this green source of energy. However, the influence of divalent ions on the performance of the technology has not been deeply studied. Basically, divalent ions are responsible for an increased membrane resistance and, therefore, for a decrease in voltage. This work focuses on the estimation of the resistance of the RED membrane working with water flows containing divalent ions, both theoretically by combining the one-thread model with the Donnan exclusion theory for the gel phase, as well as the experimental evaluation with Fumatech membranes FAS-50, FKS-50, FAS-PET-75, and FKS-PET-75. Furthermore, simulated results have been compared to data recently reported with different membranes. Besides, the influence of membrane resistance on the overall performance of reverse electrodialysis technology is evaluated to understand the impact of divalent ions in energy generation. Results reflect a minor effect of sulfate on the gross power in comparison to the effect of calcium and magnesium ions. Thus, this work takes a step forward in the knowledge of reverse electrodialysis technology and the extraction of salinity gradient energy by advancing the influence of divalent ions on energy recovery.

Physiological saline (0.9% NaCl) and deionized water were frozen in a laboratory chest freezer and impedance was monitored throughout freezing and thawing. The resistive and reactive components of electrical impedance were measured for these samples during freezing and thawing (heating) within a temperature range between 20 °C and −48 °C. The impedance of saline solution and de-ionized water increases sharply at the freezing point, similar to what is known for, e.g., complex tissues, including meat. Yet, only the saline solution impedance shows another sharp increment at a temperature between −30 and −20 °C. Changes of the electric properties after solidification suggest that the latter is linked to transformations of the ice lattice structure. We conclude that the electrical properties might serve as sensitive indicators of these phase changes.

Abstract With the ability to differentiate different molecular sizes, ion mobility spectrometry (IMS) has great potentials in the analysis of isomeric compounds. However, due to the lack of sensitivity and resolution, IMS has not been commonly used. To address the issue on resolution, the goals of this study are to explore a more effective way to perform IMS by reducing the size of ions prior to the IM measurements, and apply the new approach to the differentiation of isomeric RNA modifications. The size reduction of ribonucleoside ions was effectively accomplished by using the collision-induced dissociation process, in which the N-glycosidic bond in ribonucleoside was cleaved and split the ions into two parts—a smaller nucleobase ion and a neutral molecule of ribose sugar. Since the chemical group that corresponds to most of the RNA modifications makes up a relatively small part of the molecular structure of nucleobases, the differentiation of the dissociated nucleobase ions is expected to require a lower ion mobility resolution than the differentiation of bigger isomeric ribonucleoside ions. By using RNA methylation as a model in this study, the proposed method lowered the required resolution by 16% for the differentiation of 1-methyladenosine and N6-methyladenosine. Similar results were also obtained from the differentiation of methylated cytidine isomers. In comparison to the results obtained from using the conventional tandem mass spectrometric method, there was no significant loss of signals when the proposed method was used. The proposed method is expected to be applicable to other types of isomeric compounds. Also, the same approach is applicable on other IMS platforms.

Oil-paper insulation is the main insulating medium of converter transformers. Space charge can result in the distortion of electric field in oil-paper insulation, hence it's necessary to analyze the space charge transport characteristic and its influence on the oil-paper insulation. In the paper, the space charge transport characteristic considering the electric field is investigated, and an upstream finite element method is presented to calculate the space charge distribution in oil insulation of converter transformer considering the influence of injection barrier, ion mobility, trapped coefficient and carrier recombination coefficient. Finally, the insulation state of tortuous oil-path is evaluated. Experiments were conducted to analyze the relationship between ion mobility and electric field intensity, the results indicate that the influence of space charge on the electric field intensity in the tortuous oil-path can not be ignored for the design of converter transformer.

Atmosphere ion mobility is an important electrical parameter related to the filamentary ion flow field of high voltage direct current (HVDC) transmission lines and other characteristics of the glow and streamer corona discharge. Many machine learning (ML)-based algorithms have already been widely used in the prediction of air discharge. This article proposes a genetic algorithm (GA)-support vector regression (SVR) combined with kernel principal components analysis (PCA) to predict the ion mobility, involving dimensionality reduction, feature selection, parameter optimization of SVR. Kernel PCA could reduce the dimension of data and GA with adaptive probability parameters is employed to optimize the parameters of SVR model. An improved parallel-plates ion generator is employed to produce corona discharge and then measure the saturation ion current density and then obtain the training data and testing data of ion mobility. The prediction results show that the proposed algorithm outperforms the other methods in terms of mean relative error and mean squared error criteria. In addition, the parameters of model and data features have a major influence on the performance of the prediction algorithm. Based on the measured data and reference data, the prediction result obtained on ion mobility under different humidity shows a satisfactory generalization and effectiveness of proposed model for the prediction.

Aim: The aim of this paper is to present ion mobility spectrometry as a method for the local detection of chemical contaminants. Introduction: According to the doctrine currently in force in the Military Forces of the Republic of Poland, contamination reconnaissance is the action aimed at identifying the occurrence of chemical, biological, radiological and nuclear (CBRN) incidents or the presence of a CBRN agent in the environment. It involves observation, detection and specific contamination reconnaissance. Observation is the systematic tracking of the airspace, ground areas, people, animals and materials. Devices of visual, sound, electronic and photographic observation or other devices enabling the identification of a CBRN incident or the presence of a CBRN agent in the environment are used for that purpose. Detection is the action aimed at confirming the occurrence of a CBRN incident or the presence of a CBRN agent in the environment while specific reconnaissance is the action taken to specify the type and level of contaminants in the area once the occurrence of a CBRN incident or the presence of a CBRN agent in the environment is confirmed. Contamination reconnaissance should be prepared and performed as appropriate to the threat level. Moreover, the equipment and operating procedures employed to that end should ensure immediate alerts on the presence of CBRN agents. The current technological advancement of equipment used by fire brigades requires that fire and rescue operations take into account the careful identification of threats which may be present during the operation. The necessity for carrying out reconnaissance results from the nature of buildings under fire. While preparing measures for fighting fires of dangerous chemicals present at a given location and their properties, one should take into account chemical weapon agents (CWAs), toxic industrial chemicals (TICs), explosives, gases creating flammable or self-igniting mixtures, radioactive sources, etc. Conclusions: Contamination threats in the territory of the Republic of Poland are on an upward trend. The entities included in the National System of Contamination Detection and Alerting should be prepared, in both technical and procedural terms, for conducting reconnaissance and initial identification of contaminants at the place of their occurrence. The system is equipped with devices using ion mobility spectrometry (IMS). According to global trends, these devices should be successively replaced with solutions characterised by better sensitivity and selectivity. New devices could be based on differential mobility spectrometry (DMS). This solution should apply to portable and transportable instruments. The application of new technical solutions should be accompanied by the unification of the system in the area of contamination reconnaissance and the creation of cooperation plans, and this would have a significant impact on the safety of people and infrastructure.

Mobilization and stratification of ions and moisture in post-tensioned tendons during grout hydration can create adverse conditions which can promote corrosion. The transport of sulfate and chloride ions associated with grout segregation in large-scale tendon mockups was assessed. The grout was mixed with 15 % excess water over the manufacturers recommended limit to promote segregation and with different sulfate and chloride concentrations. The moisture content and both sulfate and chloride ion concentrations in the grout from the top sections of the tendons were significantly higher than grout from lower elevations. An ion-concentration factor (ICF) was defined as the ratio of the ion concentration in the leachate produced from the hydrated grout and the initial concentration in the grout mix water. The ion mobility in relation to moisture was analyzed in terms of the sulfate and chloride ions and their interactions with the solid and liquid phases during grout hydration.

The conversion of lignocellulosic biomass by pyrolysis or hydrothermal liquefaction gives access to a wide variety of molecules that can be used as fuel or as building blocks in the chemical industry. For such purposes, it is necessary to obtain their detailed chemical composition to adapt the conversion process, including the upgrading steps. Petroleomics has emerged as an integral approach to cover a missing link in the investigation bio-oils and linked products. It relies on ultra-high-resolution mass spectrometry to attempt to unravel the contribution of many compounds in complex samples by a non-targeted approach. The most recent developments in petroleomics partially alter the discriminating nature of the non-targeted analyses. However, a peak referring to one chemical formula possibly hides a forest of isomeric compounds, which may present a large chemical diversity concerning the nature of the chemical functions. This identification of chemical functions is essential in the context of the upgrading of bio-oils. The latest developments dedicated to this analytical challenge will be reviewed and discussed, particularly by integrating ion source features and incorporating new steps in the analytical workflow. The representativeness of the data obtained by the petroleomic approach is still an important issue.

Many experimental studies have proved that ion dynamics in a single-digit nanopore with dimensions comparable to the Debye length deviate from the bulk values, but we still have critical knowledge gaps in our understanding of ion transport in nanoconfinement. For many energy devices and sensor designs of nanoporous materials, ion mobility is a key parameter for the performance of nanofluidic equipment. However, investigating ion mobility remains an experimental challenge. This study experimentally investigated the monovalent ion dynamics of single-digit nanopores from the perspective of ionic conductance. In this article, we present a theory that is sufficient for a basic understanding of ion transport through a single-digit nanopore, and we subdivided and separately analyzed the contribution of each conductance component. These conclusions will be useful not only in understanding the behavior of ion migration but also in the design of high-performance nanofluidic devices.

Background: The COVID-19 pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has overwhelmed health systems worldwide and highlighted limitations of diagnostic testing. Several types of diagnostic tests including RT-PCR-based assays and antigen detection by lateral flow assays, each with their own strengths and weaknesses, have been developed and deployed in a short time. Methods: Here, we describe an immunoaffinity purification approach followed a by high resolution mass spectrometry-based targeted qualitative assay capable of detecting SARS-CoV-2 viral antigen from nasopharyngeal swab samples. Based on our discovery experiments using purified virus, recombinant viral protein and nasopharyngeal swab samples from COVID-19 positive patients, nucleocapsid protein was selected as a target antigen. We then developed an automated antibody capture-based workflow coupled to targeted high-field asymmetric waveform ion mobility spectrometry (FAIMS) - parallel reaction monitoring (PRM) assay on an Orbitrap Exploris 480 mass spectrometer. An ensemble machine learning-based model for determining COVID-19 positive samples was developed using fragment ion intensities from the PRM data. Findings: The optimized targeted assay, which was used to analyze 88 positive and 88 negative nasopharyngeal swab samples for validation, resulted in 98% (95% CI = 0.922–0.997) (86/88) sensitivity and 100% (95% CI = 0.958–1.000) (88/88) specificity using RT-PCR-based molecular testing as the reference method. Interpretation: Our results demonstrate that direct detection of infectious agents from clinical samples by tandem mass spectrometry-based assays have potential to be deployed as diagnostic assays in clinical laboratories, which has hitherto been limited to analysis of pure microbial cultures.

Secretions from meibomian glands located within the eyelid (commonly known as meibum) are rich in nonpolar lipid classes incorporating very-long (22–30 carbons) and ultra-long (>30 carbons) acyl chains. The complex nature of the meibum lipidome and its preponderance of neutral, nonpolar lipid classes presents an analytical challenge, with typically poor chromatographic resolution, even between different lipid classes. To address this challenge, we have deployed differential mobility spectrometry (DMS)-MS to interrogate the human meibum lipidome and demonstrate near-baseline resolution of the two major nonpolar classes contained therein, namely wax esters and cholesteryl esters. Within these two lipid classes, we describe ion mobility behavior that is associated with the length of their acyl chains and location of unsaturation. This capability was exploited to profile the molecular speciation within each class and thus extend meibum lipidome coverage. Intriguingly, structure-mobility relationships in these nonpolar lipids show similar trends and inflections to those previously reported for other physicochemical properties of lipids (e.g., melting point and phase-transition temperatures). Taken together, these data demonstrate that differential ion mobility provides a powerful orthoganol separation technology for the analysis of neutral lipids in complex matrices, such as meibum, and may further provide a means to predict physicochemical properties of lipids that could assist in inferring their biological function(s).

The hyphenation of ion mobility spectrometry with high-resolution mass spectrometry has been widely used in the characterization of various metabolites. Nevertheless, such a powerful tool remains largely unexplored in natural products research, possibly mainly due to the lack of available compounds. To evaluate the ability of collision cross-sections (CCSs) in characterizing compounds, especially isomeric natural products, here we measured and compared the traveling-wave IMS-derived nitrogen CCS values for 75 marine-derived aphidicolanes. We established a CCS database for these compounds which contained 227 CCS values of different adducts. When comparing the CCS differences, 36 of 57 pairs (over 60%) of chromatographically neighboring compounds showed a ΔCCS over 2%. What is more, 64 of 104 isomeric pairs (over 60%) of aphidicolanes can be distinguished by their CCS values, and 13 of 18 pairs (over 70%) of chromatographically indistinguishable isomers can be differentiated from the mobility dimension. Our results strongly supported CCS as an important parameter with good orthogonality and complementarity with retention time. CCS is expected to play an important role in distinguishing complex and diverse marine natural products.

Intrinsically disordered proteins (IDPs) and regions of intrinsic disorder (IDRs) are abundant in proteomes and are essential for many biological processes. Thus, they are often implicated in disease mechanisms, including neurodegeneration and cancer. The flexible nature of IDPs and IDRs provides many advantages, including (but not limited to) overcoming steric restrictions in binding, facilitating posttranslational modifications, and achieving high binding specificity with low affinity. IDPs adopt a heterogeneous structural ensemble, in contrast to typical folded proteins, making it challenging to interrogate their structure using conventional tools. Structural mass spectrometry (MS) methods are playing an increasingly important role in characterizing the structure and function of IDPs and IDRs, enabled by advances in the design of instrumentation and the development of new workflows, including in native MS, ion mobility MS, top-down MS, hydrogen-deuterium exchange MS, crosslinking MS, and covalent labeling. Here, we describe the advantages of these methods that make them ideal to study IDPs and highlight recent applications where these tools have underpinned new insights into IDP structure and function that would be difficult to elucidate using other methods.

The separation and discrete detection of isomeric sequence peptides with similar properties are important tasks for analytical science. Three different peptide isomers of 12 amino-acid residues long, containing direct and reverse regions of the alanine-valine-proline-isoleucine (AVPI) motif, were partially separated and discretely detected from their mixture using two approaches. Capillary electrophoresis enabled the separation and optical detection of the peptide sequence isomers close to the baseline. The ability to separate these sequence isomers from the mixture and discretely identify them from mass spectra has also been demonstrated by ion-mobility tandem mass spectrometry. Moreover, for the first time, capillary electrophoresis and ion-mobility mass spectrometry connected online have shown their ability for a discrete detection of the multidirectional sequence isomers.

Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical mechanisms relevant to the pathophysiology of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry technology. The investigation of plasma samples from SSc patients (n = 52) compared to a control group (n = 48) allowed us to identify four different dysfunctional metabolic mechanisms, which can be assigned to the kynurenine pathway, the urea cycle, lipid metabolism, and the gut microbiome. These significantly altered metabolic pathways are associated with inflammation, vascular damage, fibrosis, and gut dysbiosis and might be relevant for the pathophysiology of SSc. Further studies are needed to explore the role of these metabolomic networks as possible therapeutic targets of SSc.

Periodic density functional theory calculations have been performed to study the migration of various charge carriers in spinel‐type MgSc2Se4. This compound exhibits low barriers for Mg ion diffusion, making it a potential candidate for solid electrolytes in Mg-ion batteries. In order to elucidate the decisive factors for the ion mobility in spinel-type phases, the diffusion barriers of other mono- and multivalent ions (Li+, Na+, K+, Cs+, Zn2+, Ca2+, and Al3+) in the MgSc2Se4 framework have been determined as well. This allows for disentangling structural and chemical factors, showing that the ion mobility is not solely governed by size and charge of the diffusing ions. Finally, our results suggest that charge redistribution and rehybridization caused by the migration of the multivalent ions increase the resulting migration barriers.

The current status of gaseous transport studies of the singly-charged lanthanide and actinide ions is reviewed in light of potential applications to superheavy ions. The measurements and calculations for the mobility of lanthanide ions in He and Ar agree well, and they are remarkably sensitive to the electronic configuration of the ion, namely, whether the outer electronic shells are 6s, 5d6s or 6s2. The previous theoretical work is extended here to ions of the actinide family with zero electron orbital momentum: Ac+ (7s2, 1S), Am+ (5f77s 9S°), Cm+ (5f77s28S°), No+ (5f147s 2S), and Lr+ (5f147s21S). The calculations reveal large systematic differences in the mobilities of the 7s and 7s2 groups of ions and other similarities with their lanthanide analogs. The correlation of ion-neutral interaction potentials and mobility variations with spatial parameters of the electron distributions in the bare ions is explored through the ionic radii concept. While the qualitative trends found for interaction potentials and mobilities render them appealing for superheavy ion research, lack of experimental data and limitations of the scalar relativistic ab initio approaches in use make further efforts necessary to bring the transport measurements into the inventory of techniques operating in “one atom at a time” mode.

As an adaptive survival response to exogenous stress, bacteria undergo dynamic remodelling of their lipid metabolism pathways to alter the composition of their cellular membranes. Here, using Escherichia coli as a well characterised model system, we report the development and application of a ‘multi-omics’ strategy for comprehensive quantitative analysis of the temporal changes in the lipidome and proteome profiles that occur under exponential growth phase versus stationary growth phase conditions i.e., nutrient depletion stress. Lipidome analysis performed using ‘shotgun’ direct infusion-based ultra-high resolution accurate mass spectrometry revealed a quantitative decrease in total lipid content under stationary growth phase conditions, along with a significant increase in the mol% composition of total cardiolipin, and an increase in ‘odd-numbered’ acyl-chain length containing glycerophospholipids. The inclusion of field asymmetry ion mobility spectrometry was shown to enable the enrichment and improved depth of coverage of low-abundance cardiolipins, while ultraviolet photodissociation-tandem mass spectrometry facilitated more complete lipid structural characterisation compared with conventional collision-induced dissociation, including unambiguous assignment of the odd-numbered acyl-chains as containing cyclopropyl modifications. Proteome analysis using data-dependent acquisition nano-liquid chromatography mass spectrometry and tandem mass spectrometry analysis identified 83% of the predicted E. coli lipid metabolism enzymes, which enabled the temporal dependence associated with the expression of key enzymes responsible for the observed adaptive lipid metabolism to be determined, including those involved in phospholipid metabolism (e.g., ClsB and Cfa), fatty acid synthesis (e.g., FabH) and degradation (e.g., FadA/B,D,E,I,J and M), and proteins involved in the oxidative stress response resulting from the generation of reactive oxygen species during β-oxidation or lipid degradation.

Abstract Background Metabolomics represent a valuable tool to recover biological information using body fluids and may help to characterize pathophysiological mechanisms of the studied disease. This approach has not been widely used to explore inherited metabolic diseases. This study investigates mucopolysaccharidosis type III (MPS III). A thorough and holistic understanding of metabolic remodeling in MPS III may allow the development, improvement and personalization of patient care. Methods We applied both targeted and untargeted metabolomics to urine samples obtained from a French cohort of 49 patients, consisting of 13 MPS IIIA, 16 MPS IIIB, 13 MPS IIIC, and 7 MPS IIID, along with 66 controls. The analytical strategy is based on ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Twenty-four amino acids have been assessed using tandem mass spectrometry combined with liquid chromatography. Multivariate data modeling has been used for discriminant metabolite selection. Pathway analysis has been performed to retrieve metabolic pathways impairments. Results Data analysis revealed distinct biochemical profiles. These metabolic patterns, particularly those related to the amino acid metabolisms, allowed the different studied groups to be distinguished. Pathway analysis unveiled major amino acid pathways impairments in MPS III mainly arginine–proline metabolism and urea cycle metabolism. Conclusion This represents one of the first metabolomics-based investigations of MPS III. These results may shed light on MPS III pathophysiology and could help to set more targeted studies to infer the biomarkers of the affected pathways, which is crucial for rare conditions such as MPS III.

Infection by the human noroviruses (hNoV), for the vast majority of strains, requires attachment of the viral capsid to histo blood group antigens (HBGAs). The HBGA-binding pocket is formed by dimers of the protruding domain (P dimers) of the capsid protein VP1. Several studies have focused on HBGA binding to P dimers, reporting binding affinities and stoichiometries. However, nuclear magnetic resonance spectroscopy (NMR) and native mass spectrometry (MS) analyses yielded incongruent dissociation constants (KD) for the binding of HBGAs to P dimers and, in some cases, disagreed on whether glycans bind at all. We hypothesized that glycan clustering during electrospray ionization in native MS critically depends on the physicochemical properties of the protein studied. It follows that the choice of a reference protein is crucial. We analysed carbohydrate clustering using various P dimers and eight non-glycan binding proteins serving as possible references. Data from native and ion mobility MS indicate that the mass fraction of β-sheets has a strong influence on the degree of glycan clustering. Therefore, the determination of specific glycan binding affinities from native MS must be interpreted cautiously.

This paper aims to cover the main strategies based on ion mobility spectrometry (IMS) for the analysis of biological samples. The determination of endogenous and exogenous compounds in such samples is important for the understanding of the health status of individuals. For this reason, the development of new approaches that can be complementary to the ones already established (mainly based on liquid chromatography coupled to mass spectrometry) is welcomed. In this regard, ion mobility spectrometry has appeared in the analytical scenario as a powerful technique for the separation and characterization of compounds based on their mobility. IMS has been used in several areas taking advantage of its orthogonality with other analytical separation techniques, such as liquid chromatography, gas chromatography, capillary electrophoresis, or supercritical fluid chromatography. Bioanalysis is not one of the areas where IMS has been more extensively applied. However, over the last years, the interest in using this approach for the analysis of biological samples has clearly increased. This paper introduces the reader to the principles controlling the separation in IMS and reviews recent applications using this technique in the field of bioanalysis.

The atmospheric oxidation of monoterpenes leads to the formation of secondary organic aerosol (SOA). While numerous works have been carried out in the past to characterise SOA at a molecular level, the structural elucidation of SOA compounds remains challenging owing to the lack of authentic standard compounds. In this work, the structures of α-pinene originating dimeric esters in SOA with m/z 357 (C17H25O8-) and m/z 367 (C19H27O7-) were characterised using UPLC/ESI(-)IMS-TOFMS2 (ultra-performance liquid chromatography coupled to ion mobility spectrometry tandem time-of-flight mass spectrometry). The measured collision cross-section (ΩN2) values were compared to theoretically calculated ΩN2 values. Selected product ions of dimeric compounds and the authentic standard compounds of product ions were subjected to CO2-IMS-TOFMS for more detailed structural characterisation. Our results were consistent with previously reported subunits of the m/z 357 (terpenylic acid and cis-pinic acid), and the m/z 367 (10-hydroxy-cis-pinonic acid and cis-pinic acid) ions. The measured and calculated ΩN2 values of m/z 367 ions further support the conclusion of earlier structural characterisation; however, the structure of the m/z 357 ion remains vague and requires further characterisation studies with a synthesised reference compound.

Hysteresis in perovskite solar cells is a notorious issue limiting its development in stability, reproducibility and efficiency. Ions’ migration coupled with charges’ recombination are indispensable factors to generate the hysteretic curves on the basis of experimental and theoretical calculation studies, however, the underlying physical characteristics are rarely clarified. Here, a mixed electronic-ionic drift-diffusion model combined with bulk and interfacial recombination is investigated. Positive and negative ion species could drift to and accumulate at interfaces between the perovskite/transport layers, influencing internal electric potential profiles and delaying the charges’ ejection to the transport layers. The charges might recombine spontaneously or trap-assisted, reducing the total amount of electrons and holes collected in the external circuit, leading to a diminished photocurrent. Moreover, our calculations indicate that an appropriate measurement protocol is really essential to evaluate the device performance precisely and to suppress J–V hysteresis. Meanwhile, a negligible hysteretic loop could be obtained by balancing the material properties of the transport layers and restraining the ions mobility in the perovskite layer.

Lipidomics has great promise in various applications; however, a major bottleneck in lipidomics is the accurate and comprehensive annotation of high-resolution tandem mass spectral data. While the number of available lipidomics software has drastically increased over the past five years, the reduction of false positives and the realization of obtaining structurally accurate annotations remains a significant challenge. We introduce Lipid Annotator, which is a user-friendly software for lipidomic analysis of data collected by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). We validate annotation accuracy against lipid standards and other lipidomics software. Lipid Annotator was integrated into a workflow applying an iterative exclusion MS/MS acquisition strategy to National Institute of Standards and Technology (NIST) SRM 1950 Metabolites in Frozen Human Plasma using reverse phase LC-HRMS/MS. Lipid Annotator, LipidMatch, and MS-DIAL produced consensus annotations at the level of lipid class for 98% and 96% of features detected in positive and negative mode, respectively. Lipid Annotator provides percentages of fatty acyl constituent species and employs scoring algorithms based on probability theory, which is less subjective than the tolerance and weighted match scores commonly used by available software. Lipid Annotator enables analysis of large sample cohorts and improves data-processing throughput as compared to previous lipidomics software.

Research in toxinology has created a pharmacological paradox. With an estimated 220,000 venomous animals worldwide, the study of peptidyl toxins provides a vast number of effector molecules. However, due to the complexity of the protein-protein interactions, there are fewer than ten venom-derived molecules on the market. Structural characterization and identification of post-translational modifications are essential to develop biological lead structures into pharmaceuticals. Utilizing advancements in mass spectrometry, we have created a high definition approach that fuses conventional high-resolution MS-MS with ion mobility spectrometry (HDMSE) to elucidate these primary structure characteristics. We investigated venom from ten species of “tiger” spider (Genus: Poecilotheria) and discovered they contain isobaric conformers originating from non-enzymatic Asp isomerization. One conformer pair conserved in five of ten species examined, denominated PcaTX-1a and PcaTX-1b, was found to be a 36-residue peptide with a cysteine knot, an amidated C-terminus, and isoAsp33Asp substitution. Although the isomerization of Asp has been implicated in many pathologies, this is the first characterization of Asp isomerization in a toxin and demonstrates the isomerized product’s diminished physiological effects. This study establishes the value of a HDMSE approach to toxin screening and characterization.

The main insulation of converter transformers consists of transformer oil and oil-impregnated pressboard. Under operating conditions, the valve-side winding of the converter transformer is subject to DC voltage components. Therefore, studies on the characteristics of oil-impregnated pressboard conductivity are necessary. In this paper, the temperature, moisture and electric field dependency of pressboard conductivity are investigated based on a specially designed three-electrode experimental chamber, which allows for a variation in temperature ranging from 25 °C to 120 °C and an electric field strength ranging from 0 to 30 kV/mm. The experimental results show that, within the experimental conditions, the conductivity of oil-impregnated pressboard increases exponentially with increasing moisture and temperature. High moisture and temperature will increase both the carrier concentration and carrier mobility, which explains the exponential correspondence. Furthermore, the electric field dependency of the conductivity is more obvious for wet pressboard than for dry pressboard. Protons in the wet pressboard are more easily accelerated by the electric field than the impurity ions in the oil of the dry pressboard, which leads to an obvious electric field dependency of the wet pressboard conductivity.

Thiolate-protected metal nanoclusters have highly size- and structure-dependent physicochemical properties and are a promising class of nanomaterials. As a consequence, for the rationalization of their synthesis and for the design of new clusters with tailored properties, a precise characterization of their composition and structure at the atomic level is required. We report a combined ion mobility-mass spectrometry approach with density functional theory (DFT) calculations for determination of the structural and optical properties of ultra-small gold nanoclusters protected by thioglycolic acid (TGA) as ligand molecules, Au10(TGA)10. Collision cross-section (CCS) measurements are reported for two charge states. DFT optimized geometrical structures are used to compute CCSs. The comparison of the experimentally- and theoretically-determined CCSs allows concluding that such nanoclusters have catenane structures.

We present electrowinning of silver (Ag) from crystalline silicon (c-Si) solar cells using a solution of methanesulfonic acid (MSA) as the electrolyte. Ag dissolved effectively in MSA because of its high solubility in MSA; however, the electrochemical recovery of Ag from MSA solutions was found to be inefficient because of the low mobility of Ag ions in MSA, owing to its high viscosity. Therefore, we decreased the viscosity of MSA by adding deionized (DI) water, as a possible method for enhancing the mobility of Ag ions. The concentrations of added DI water were 0, 1.1, 5.0, 9.3, and 20.8 M, respectively. Further, we performed cyclic voltammetry for each solution to calculate the diffusion coefficient using the Randles⁻Sevcik equation, and analyzed the viscosity of MSA solutions depending on the concentration of added water using a rheometer. The morphologies of the electrochemically recovered Ag particles changed with variations in the amount of the added water, from branch-like structures to dendritic structures with a decreasing size. Moreover, the cathodic current efficiency increased considerably with increasing concentration of the added DI water. Finally, we recovered Ag with >99.9% (3N) purity from c-Si solar cells by electrowinning, as determined by glow discharge mass spectrometry.

Este trabalho objetivou avaliar o efeito da calagem e sua influência sobre atributos químicos e de fauna do solo em um Cambissolo sob sistema de semeadura direta. O experimento vem sendo conduzido em Lages, SC, desde maio de 2001. Os tratamentos foram: semeadura direta com calcário incorporado na dose de 1 SMP (SD-inc) e superficial nas doses de 1/5 SMP (SD-1/5sup) e 1/2 SMP (SD-1/2sup). Como padrão, utilizou-se solo sem cultivo e sem aplicação de calcário, e uma área de pastagem perene com calcário incorporado na dose de 1 SMP (PI-inc). O solo foi amostrado nas camadas de 0-5; 5-10; 10-20cm para análise de Ca2+, Mg+2, Al3+, pH em água e em CaCl2; e de 0-10cm para carbono orgânico total e fauna do solo. A aplicação superficial de calcário no sistema de semeadura direta na maior dose (1/2 SMP) elevou os teores de Ca2+ até 10cm de profundidade e de Mg+2 até a camada de 10 a 20cm. A abundância e a diversidade da fauna edáfica foram maiores nas áreas sob semeadura direta e pastagem, em relação ao solo sem cultivo, mostrando sensibilidade às alterações advindas do manejo do solo, mas sem correlação direta com as modificações químicas decorrentes da calagem.This research was aimed at evaluating the effect of liming and its influence on chemistry and fauna properties of a Cambisol under no-tillage system. The experiment has been carried out in Lages, SC, southern Brazil, since May 2001. The treatments were: no-tillage with incorporated lime in the rate of 1 SMP (NT-inc); superficial liming in the rate of 1/5 SMP (NT-1/5sup), and 1/2 SMP (NT-1/2sup). As control treatment, bare soil without cultivation without lime application (BS), and plots with perennial pasture with incorporate lime in the rate of 1 SMP (Pp-inc) were used. Soil samples were collected in the layers of 0-5; 5-10; 10-20cm depth for analysis of Ca2+, Mg+2, Al3+, water and CaCl2 pH. Total organic carbon and soil fauna were analysed in the layer 0-10cm. The superficial liming in the no-tillage system in the highest rate (1/2 SMP) increased Ca2+ contents up to 10 cm depth and Mg+2 up to the layer of 10 to 20cm. The abundance and diversity of soil fauna were higher in cultivated plots under no-tillage and pasture, in relation to the bare soil, showing influences of soil management, but with no direct relation with chemical soil conditions created by liming.

Twenty-eight sponge specimens were collected at a shallow water hydrothermal vent site north of Iceland. Extracts were prepared and tested in vitro for cytotoxic activity, and eight of them were shown to be cytotoxic. A mass spectrometry (MS)-based metabolomics approach was used to determine the chemical composition of the extracts. This analysis highlighted clear differences in the metabolomes of three sponge specimens, and all of them were identified as Haliclona (Rhizoniera) rosea (Bowerbank, 1866). Therefore, these specimens were selected for further investigation. Haliclona rosea metabolomes contained a class of potential key compounds, the 3-alkyl pyridine alkaloids (3-APA) responsible for the cytotoxic activity of the fractions. Several 3-APA compounds were tentatively identified including haliclamines, cyclostellettamines, viscosalines and viscosamines. Among these compounds, cyclostellettamine P was tentatively identified for the first time by using ion mobility MS in time-aligned parallel (TAP) fragmentation mode. In this work, we show the potential of applying metabolomics strategies and in particular the utility of coupling ion mobility with MS for the molecular characterization of sponge specimens.

Hadamard transform atmospheric pressure ion mobility-MS and rapid UHPLC-MS methods were investigated for analysis of closely related isomeric flavonoids and their glycosides using a test set of seven standards. On a time scale of a few minutes, the flavonoid aglycones were all separated by ion mobility, but not by UHPLC. The glycosides were better resolved by IMS but not completely separated by both methods. The results suggest that IMS provides sufficient resolution for separation of isomeric polyphenols such as flavonoids in high-throughput metabolomics studies.

The identification of compounds in complex mixtures remains challenging despite recent advances in analytical techniques. At present, no single method can detect and quantify the vast array of compounds that might be of potential interest in metabolomics studies. High performance liquid chromatography/mass spectrometry (HPLC/MS) is often considered the analytical method of choice for analysis of biofluids. The positive identification of an unknown involves matching at least two orthogonal HPLC/MS measurements (exact mass, retention index, drift time etc.) against an authentic standard. However, due to the limited availability of authentic standards, an alternative approach involves matching known and measured features of the unknown compound with computationally predicted features for a set of candidate compounds downloaded from a chemical database. Computationally predicted features include retention index, ECOM50 (energy required to decompose 50% of a selected precursor ion in a collision induced dissociation cell), drift time, whether the unknown compound is biological or synthetic and a collision induced dissociation (CID) spectrum. Computational predictions are used to filter the initial “bin” of candidate compounds. The final output is a ranked list of candidates that best match the known and measured features. In this mini review, we discuss cheminformatics methods underlying this database search-filter identification approach.

The identification of compounds in complex mixtures remains challenging despite recent advances in analytical techniques. At present, no single method can detect and quantify the vast array of compounds that might be of potential interest in metabolomics studies. High performance liquid chromatography/mass spectrometry (HPLC/MS) is often considered the analytical method of choice for analysis of biofluids. The positive identification of an unknown involves matching at least two orthogonal HPLC/MS measurements (exact mass, retention index, drift time etc.) against an authentic standard. However, due to the limited availability of authentic standards, an alternative approach involves matching known and measured features of the unknown compound with computationally predicted features for a set of candidate compounds downloaded from a chemical database. Computationally predicted features include retention index, ECOM50 (energy required to decompose 50% of a selected precursor ion in a collision induced dissociation cell), drift time, whether the unknown compound is biological or synthetic and a collision induced dissociation (CID) spectrum. Computational predictions are used to filter the initial “bin” of candidate compounds. The final output is a ranked list of candidates that best match the known and measured features. In this mini review, we discuss cheminformatics methods underlying this database search-filter identification approach.