100,228 results on '"ion mobility"'
Search Results
2. Single ion mobility monitoring (SIM2) stitching method for high-throughput and high ion mobility resolution chiral analysis
- Author
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Chalet, Clément, Rathahao-Paris, Estelle, and Alves, Sandra
- Published
- 2024
- Full Text
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3. High-resolution ion mobility based on traveling wave structures for lossless ion manipulation resolves hidden lipid features
- Author
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Reardon, Allison R., May, Jody C., Leaptrot, Katrina L., and McLean, John A.
- Published
- 2024
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4. Rapid analysis of pesticide residues in polished rice using modified QuEChERS method combined with ion mobility spectrometry and partial least squares regression techniques
- Author
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Zhu, Jiayi, Liu, Hanchi, Huang, Yuxiao, Huan, Yingying, Zhang, Zhengyong, Zhang, Ding, and Sha, Min
- Published
- 2024
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5. Rapid separation of bile acid isomers via ion mobility mass spectrometry by complexing with spiramycin
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Zhang, Manli, Pan, Yao, Feng, Shugai, Chi, Chaoxian, Wu, Fangling, and Ding, Chuan-Fan
- Published
- 2024
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6. Recent additions and access to a multidimensional lipidomic database containing liquid chromatography, ion mobility spectrometry, and tandem mass spectrometry information
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Solosky, Amie M., Kirkwood-Donelson, Kaylie I., Odenkirk, Melanie T., and Baker, Erin S.
- Published
- 2024
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7. Headspace-Gas Chromatography-Ion Mobility Spectrometry Provides New Insights into Aroma Differences and the “Increasing Fragrance over Time” Phenomenon of Lysimachia foenum-graecum Hance
- Author
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Qin, You, Kuang, Minghao, Zhao, He, Mai, Huiqi, Cai, Ping, and Zhang, Shuihan
- Published
- 2024
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8. Dependency of fentanyl analogue protomer ratios on solvent conditions as measured by ion mobility-mass spectrometry.
- Author
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Johnson CR, Sabatini HM, Aderorho R, and Chouinard CD
- Subjects
- Hydrogen-Ion Concentration, Spectrometry, Mass, Electrospray Ionization methods, Isomerism, Methanol chemistry, Acetonitriles chemistry, Tandem Mass Spectrometry methods, Water chemistry, Fentanyl analogs & derivatives, Fentanyl chemistry, Fentanyl analysis, Solvents chemistry, Ion Mobility Spectrometry methods
- Abstract
Recently, our group has shown that fentanyl and many of its analogues form prototropic isomers ("protomers") during electrospray ionization. These different protomers can be resolved using ion mobility spectrometry and annotated using mobility-aligned tandem mass spectrometry fragmentation. However, their formation and the extent to which experimental variables contribute to their relative ratio remain poorly understood. In the present study, we systematically investigated the effects of mixtures of common chromatographic solvents (water, methanol, and acetonitrile) and pH on the ratio of previously observed protomers for 23 fentanyl analogues. Interestingly, these ratios (N-piperidine protonation vs. secondary amine/O = protonation) decreased significantly for many analogues (e.g., despropionyl ortho-, meta-, and para-methyl fentanyl), increased significantly for others (e.g., cis-isofentanyl), and remained relatively constant for the others as solvent conditions changed from 100% organic solvent (methanol or acetonitrile) to 100% water. Interestingly, pH also had significant effects on this ratio, causing the change in ratio to switch in many cases. Lastly, increasing conditions to pH ≥ 4.0 also prompted the appearance of new mobility peaks for ortho- and para-methyl acetyl fentanyl, where all previous studies had only showed one single distribution. Because these ratios have promise to be used qualitatively for identification of these (and emerging) fentanyl analogues, understanding how various conditions (i.e., mobile phase selection and/or chromatographic gradient) affect their ratios is critically important to the development of advanced ion mobility and mass spectrometry methodologies to identify fentanyl analogues., (© 2024 The Author(s). Journal of Mass Spectrometry published by John Wiley & Sons Ltd.)
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- 2024
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9. Pursuing drug laboratories: Analysis of drug precursors with High Kinetic Energy Ion Mobility Spectrometry.
- Author
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Schaefer C, Lippmann M, Schindler C, Beukers M, Beijer N, Hitzemann M, van de Kamp B, Peters R, Knotter J, and Zimmermann S
- Subjects
- Humans, Methamphetamine analysis, Amphetamine analysis, Forensic Toxicology methods, Ion Mobility Spectrometry methods
- Abstract
High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS) is a technique for rapid and reliable detection of trace compounds down to ppb
V -levels within one second. Compared to classical IMS operating at ambient pressure and providing the ion mobility at low electric fields, HiKE-IMS can also provide the analyte-specific field dependence of the ion mobility and a fragmentation pattern at high reduced electric field strengths. The additional information about the analyte obtained by varying the reduced electric field strength can contribute to reliable detection. Furthermore, the reduced number of ion-molecule reactions at the low operating pressure of 10 - 40 mbar and the shorter reaction times reduce the impact of competing ion-molecule reactions that can cause false negatives. In this work, we employ HiKE-IMS for the analysis of phenyl-2-propanone (P2P) and other precursor chemicals used for synthesis of methamphetamine and amphetamine. The results show that the precursor chemicals exhibit different behavior in HiKE-IMS. Some precursors form a single significant ion species, while others readily form a fragmentation pattern. Nevertheless, all drug precursors can be distinguished from each other, from the reactant ions and from interfering compounds. In particular, the field-dependent ion mobility as an additional separation dimension aids identification, potentially reducing the number of false positive alarms in field applications. Furthermore, the analysis of a seized illicit P2P sample shows that even low levels of P2P can be detected despite the complex background present in the headspace of real samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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10. A stepwise surface ionization method for ion mobility spectrometry.
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Lin J, Gao X, Jia J, and He X
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- Humans, Humidity, Ions analysis, Ions chemistry, Ion Mobility Spectrometry methods, Breath Tests methods, Methylamines analysis
- Abstract
Rationale: The detection of organic nitrogen compounds in exhaled breath is expected to provide an early warning of diseases such as kidney disease. Detecting these trace disease markers in exhaled breath with complex composition and high moisture content is a challenge. Surface ionization (SI) shows a highly selective ionization of organic nitrogen compounds, and it is a good candidate for breath analysis combined with ion mobility spectrometry (IMS)., Methods: A stepwise SI method of low-temperature adsorption/high-temperature ionization was proposed, and trimethylamine (TMA) was detected when combined with an ion mobility spectrometer. TMA at different concentrations and humidity levels and spiked in human breath was detected to evaluate the method's properties., Results: TMA with concentrations from 2 to 200 ppb was detected. The peak intensity of the TMA characteristic ions was linearly related to the "e" exponent of the concentration with a curve fit of 0.996. A standard deviation of less than 0.306% was obtained with 10 replicate analyses of 10 ppb TMA. The signal intensity difference between dry and wet (relative humidity > 93%) TMA samples is only 2.7%, and the recovery rate of the sample was 106.819%., Conclusions: SI-IMS based on the stepwise SI method has the advantages of low ionization temperature, high detection sensitivity, strong resistance to humidity interference, and good repeatability. It is a promising method for detecting organic nitrogen compounds in exhaled breath., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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11. Letter to the editor for the article "Pilot study for bladder cancer detection with volatile organic compounds using ion mobility spectrometry: a novel urine-based approach".
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Duquesne I, Vordos D, and de la Taille A
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- Humans, Pilot Projects, Urinary Bladder Neoplasms urine, Urinary Bladder Neoplasms diagnosis, Volatile Organic Compounds urine, Ion Mobility Spectrometry methods
- Published
- 2024
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12. Bottom-up Histone Post-translational Modification Analysis using Liquid Chromatography, Trapped Ion Mobility Spectrometry, and Tandem Mass Spectrometry.
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Fuller CN, Valadares Tose L, Vitorino FNL, Bhanu NV, Panczyk EM, Park MA, Garcia BA, and Fernandez-Lima F
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- Humans, Chromatography, Liquid methods, Proteomics methods, Amino Acid Sequence, Reproducibility of Results, Cell Line, Tumor, Molecular Sequence Data, Protein Processing, Post-Translational, Tandem Mass Spectrometry methods, Histones chemistry, Histones analysis, Ion Mobility Spectrometry methods
- Abstract
The amino acid position within a histone sequence and the chemical nature of post-translational modifications (PTMs) are essential for elucidating the "Histone Code". Previous work has shown that PTMs induce specific biological responses and are good candidates as biomarkers for diagnostics. Here, we evaluate the analytical advantages of trapped ion mobility (TIMS) with parallel accumulation-serial fragmentation (PASEF) and tandem mass spectrometry (MS/MS) for bottom-up proteomics of model cancer cells. The study also considered the use of nanoliquid chromatography (LC) and traditional methods: LC-TIMS-PASEF-ToF MS/MS vs nLC-TIMS-PASEF-ToF MS/MS vs nLC-MS/MS. The addition of TIMS and PASEF-MS/MS increased the number of detected peptides due to the added separation dimension. All three methods showed high reproducibility and low RSD in the MS domain (<5 ppm). While the LC, nLC and TIMS separations showed small RSD across samples, the accurate mobility (1/K
0 ) measurements (<0.6% RSD) increased the confidence of peptide assignments. Trends were observed in the retention time and mobility concerning the number and type of PTMs (e.g., ac, me1-3 ) and their corresponding unmodified, propionylated peptide that aided in peptide assignment. Mobility separation permitted the annotation of coeluting structural and positional isomers and compared with nLC-MS/MS showed several advantages due to reduced chemical noise.- Published
- 2024
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13. Introducing Ion Mobility Mass Spectrometry in Brain Glycosaminoglycomics: Application to Chondroitin/Dermatan Sulfate Octasaccharide Domains.
- Author
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Sarbu M, Seidler DG, Clemmer DE, and Zamfir AD
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- Animals, Brain metabolism, Glycomics methods, Dermatan Sulfate analysis, Dermatan Sulfate chemistry, Chondroitin Sulfates analysis, Chondroitin Sulfates chemistry, Ion Mobility Spectrometry methods, Tandem Mass Spectrometry methods, Brain Chemistry, Oligosaccharides analysis, Oligosaccharides chemistry
- Abstract
Glycosaminoglycans (GAGs) are sulfated linear O -glycan chains abundantly expressed in the extracellular matrix (ECM). Among GAGs, chondroitin sulfate (CS) and dermatan sulfate (DS) play important roles at the brain level, where the distribution and location of the sulfates within the CS/DS chains are responsible for numerous biological events. The diversity of the neural hybrid CS/DS expressed in the brain and the need to elucidate their structure gave rise to considerable efforts toward the development of analytical methods able to discover novel regularly and irregularly sulfated domains. In this context, we report here the introduction of ion mobility separation (IMS) mass spectrometry (MS) in brain glycosaminoglycomics. Based on IMS MS and tandem MS (MS/MS) by collision-induced dissociation (CID), we have developed a powerful approach for the screening and structural analysis of neural CS/DS and optimized and validated the method for the structural analysis of octasaccharides that were released from brain proteoglycans by β-elimination and pooled after chain depolymerization using chondroitin AC lyase. The IMS MS data revealed the separation of CS/DS octamers into mobility families based on the amount of sulfation. Among the discovered oversulfated domains, of major biological importance is the pentasulfated-[4,5-Δ-GlcAGalNAc(IdoAGalNAc)
3 ], for which the (-) nanoESI IMS CID MS/MS analysis disclosed through the presence of distinct drift times, the incidence of two isomers. Moreover, the generated fragment ions revealed an uncommon trisulfated motif and an uncommon pentasulfated motif. Hence, using IMS MS and CID MS/MS, novel brain-related CS/DS domains of atypical sulfation patterns were discovered and structurally characterized in detail.- Published
- 2024
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14. Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.
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Dai Z, Ben-Younis A, Vlachaki A, Raleigh D, and Thalassinos K
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- Humans, Islet Amyloid Polypeptide chemistry, Islet Amyloid Polypeptide metabolism, Mass Spectrometry, Ion Mobility Spectrometry
- Abstract
Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to β-cell death in pancreatic islets and are considered a hallmark of Type II diabetes Mellitus (T2DM). Evidence suggests that the early oligomers of hIAPP formed during the aggregation process are the primary pathological agent in islet amyloid induced β-cell death. The self-assembly mechanism of hIAPP, however, remains elusive, largely due to limitations in conventional biophysical techniques for probing the distribution or capturing detailed structures of the early, structurally dynamic oligomers. The advent of Ion-mobility Mass Spectrometry (IM-MS) has enabled the characterisation of hIAPP early oligomers in the gas phase, paving the way towards a deeper understanding of the oligomerisation mechanism and the correlation of structural information with the cytotoxicity of the oligomers. The sensitivity and the rapid structural characterisation provided by IM-MS also show promise in screening hIAPP inhibitors, categorising their modes of inhibition through "spectral fingerprints". This review delves into the application of IM-MS to the dissection of the complex steps of hIAPP oligomerisation, examining the inhibitory influence of metal ions, and exploring the characterisation of hetero-oligomerisation with different hIAPP variants. We highlight the potential of IM-MS as a tool for the high-throughput screening of hIAPP inhibitors, and for providing insights into their modes of action. Finally, we discuss advances afforded by recent advancements in tandem IM-MS and the combination of gas phase spectroscopy with IM-MS, which promise to deliver a more sensitive and higher-resolution structural portrait of hIAPP oligomers. Such information may help facilitate a new era of targeted therapeutic strategies for islet amyloidosis in T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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15. Waste Point Identification of Frying Oil Based on Gas Chromatography-Ion Mobility Spectrometry (GC-IMS).
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Ye L, Song L, Zhang L, and Cui R
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- Gas Chromatography-Mass Spectrometry methods, Principal Component Analysis, Cooking, Cottonseed Oil chemistry, Hot Temperature, Ion Mobility Spectrometry methods, Volatile Organic Compounds analysis, Volatile Organic Compounds chemistry
- Abstract
This study described the quality detection and rapid identification of frying oil waste points based on gas chromatography-ion mobility spectrometry (GC-IMS). A total of 48 volatile substances were identified, among which the levels of 11 components, including 2-pentylfuran, 2-butylfuran, and 2-hexanone, increased with prolonged frying time after 40 h in cottonseed oil. Conversely, the levels of hexanal, heptanal, and E,E-2,4-heptadienal decreased as frying time extended. Correlation analysis revealed a significant association between volatile substances of the oil and acid value ( p < 0.05) and polar components with volatile substances ( p < 0.05). Furthermore, significant differences in the types and contents of flavor substances were observed in cottonseed oil at different frying times (including before and after reaching the discard point) ( p < 0.05). Subsequently, principal component analysis (PCA) results clearly showed that the cottonseed oil samples at different frying times were well distinguished by the volatile compounds; moreover, discriminant model analysis indicated a model accuracy rate of 100%. These results showed the potential of GC-IMS-based approaches in discriminating the waste points of frying oil.
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- 2024
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16. Distinguishing Isomeric Cyclobutane Thymidine Dimers by Ion Mobility and Tandem Mass Spectrometry.
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Yang HC, Scruggs SS, Chai M, Mathai G, Taylor JS, and Gross ML
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- Isomerism, DNA chemistry, Cyclobutanes chemistry, Thymidine chemistry, Tandem Mass Spectrometry methods, Pyrimidine Dimers chemistry, Pyrimidine Dimers analysis, Ion Mobility Spectrometry methods
- Abstract
Irradiation of the major conformation of duplex DNA found in cells (B form) produces cyclobutane pyrimidine dimers (CPDs) from adjacent pyrimidines in a head-to-head orientation ( syn ) with the C5 substituents in a cis stereochemistry. These CPDs have crucial implications in skin cancer. Irradiation of G-quadruplexes and other non-B DNA conformations in vitro produces, however, CPDs between nonadjacent pyrimidines in nearby loops with syn and head-to-tail orientations ( anti ) with both cis and trans stereochemistry to yield a mixture of six possible isomers of the T=T dimer. This outcome is further complicated by formation of mixtures of nonadjacent CPDs of C=T, T=C, and C=C, and successful analysis depends on development of specific and sensitive methods. Toward meeting this need, we investigated whether ion mobility mass spectrometry (IMMS) and MS/MS can distinguish the cis,syn and trans,anti T=T CPDs. Ion mobility can afford baseline separation and give relative mobilities that are in accord with predicted cross sections. Complementing this ability to distinguish isomers is MS/MS collisional activation where fragmentation also distinguishes the two isomers and confirms conclusions drawn from ion mobility analysis. The observations offer early support that ion mobility and MS/MS can enable the distinction of DNA photoproduct isomers.
- Published
- 2024
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17. Enhanced Declustering Enables Native Top-Down Analysis of Membrane Protein Complexes using Ion-Mobility Time-Aligned Fragmentation.
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Sokratous K, Cooper-Shepherd DA, Ujma J, Qu F, Giles K, Ben-Younis A, Hensen M, Langridge JI, Gault J, Jazayeri A, Liko I, and Hopper JTS
- Subjects
- Micelles, Mass Spectrometry methods, Detergents chemistry, Ions chemistry, Membrane Proteins chemistry, Membrane Proteins analysis, Ion Mobility Spectrometry methods
- Abstract
Native mass spectrometry (MS) is proving to be a disruptive technique for studying the interactions of proteins, necessary for understanding the functional roles of these biomolecules. Recent research is expanding the application of native MS towards membrane proteins directly from isolated membrane preparations or from purified detergent micelles. The former results in complex spectra comprising several heterogeneous protein complexes; the latter enables therapeutic protein targets to be screened against multiplexed preparations of compound libraries. In both cases, the resulting spectra are increasingly complex to assign/interpret, and the key to these new directions of native MS research is the ability to perform native top-down analysis, which allows unambiguous peak assignment. To achieve this, detergent removal is necessary prior to MS analyzers, which allow selection of specific m / z values, representing the parent ion for downstream activation. Here, we describe a novel, enhanced declustering (ED) device installed into the first pumping region of a cyclic IMS-enabled mass spectrometry platform. The device enables declustering of ions prior to the quadrupole by imparting collisional activation through an oscillating electric field applied between two parallel plates. The positioning of the device enables liberation of membrane protein ions from detergent micelles. Quadrupole selection can now be utilized to isolate protein-ligand complexes, and downstream collision cells enable the dissociation and identification of binding partners. We demonstrate that ion mobility (IM) significantly aids in the assignment of top-down spectra, aligning fragments to their corresponding parent ions by means of IM drift time. Using this approach, we were able to confidently assign and identify a novel hit compound against Pf MATE, obtained from multiplexed ligand libraries.
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- 2024
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18. Development of a cyclic ion mobility spectrometry-mass spectrometry-based collision cross-section database of permethylated human milk oligosaccharides.
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Habibi SC, Bradford VR, Baird SC, Lucas SW, Chouinard CD, and Nagy G
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- Humans, Methylation, Isomerism, Tandem Mass Spectrometry methods, Mass Spectrometry methods, Databases, Factual, Milk, Human chemistry, Ion Mobility Spectrometry methods, Oligosaccharides analysis, Oligosaccharides chemistry
- Abstract
Human milk oligosaccharides (HMOs) are an important class of biomolecules responsible for the healthy development of the brain-gut axis of infants. Unfortunately, their accurate characterization is largely precluded due to a variety of reasons - there are over 200 possible HMO structures whereas only 10s of these are available as authentic analytical standards. Furthermore, their isomeric heterogeneity stemming from their many possible glycosidic linkage positions and corresponding α/β anomericities further complicates their analyses. While liquid chromatography coupled to tandem mass spectrometry remains the gold standard for HMO analyses, it often times cannot resolve all possible isomeric species and thus warrants the development of other orthogonal approaches. High-resolution ion mobility spectrometry coupled to mass spectrometry has emerged as a rapid alternative to condensed-phase separations but largely has remained limited to qualitative information related to the resolution of isomers. In this work, we have assessed the use of permethylation to improve both the resolution and sensitivity of HMO analyses with cyclic ion mobility separations coupled with mass spectrometry. In addition to this, we have developed the first-ever high-resolution collision cross-section database for permethylated HMOs using our previously established calibration protocol. We envision that this internal reference database generated from high-resolution cyclic ion mobility spectrometry-mass spectrometry will greatly aid in the accurate characterization of HMOs and provide a valuable, orthogonal, approach to existing liquid chromatography-tandem mass spectrometry-based methods., (© 2024 The Author(s). Journal of Mass Spectrometry published by John Wiley & Sons Ltd.)
- Published
- 2024
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19. Atmospheric pressure field desorption-trapped ion mobility-mass spectrometry coupling
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Gross, Jürgen H.
- Published
- 2024
- Full Text
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20. Rapid quantification of disaccharide isomers by derivatization in combination with ion mobility spectrometry in beer and milk.
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Ye K, Ye J, Yan Y, and Ding CF
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- Isomerism, Animals, Lactose chemistry, Lactose analysis, Maltose analysis, Maltose chemistry, Benzoates chemistry, Ion Mobility Spectrometry methods, Beer analysis, Milk chemistry, Disaccharides chemistry, Disaccharides analysis
- Abstract
The subtle structural variations among carbohydrate isomers pose significant challenges for their identification and quantification. Here, we propose a strategy for rapid identification and quantification of isomeric disaccharides via derivatization with 4-(3-methyl-5-oxo-pyrazolin-1-yl) benzoic acid (CPMP) and analysing by ion mobility spectrometry (IMS). After derivatization, the ionization efficiency of disaccharides was significantly improved. The disaccharide isomers were distinguished by determining the different ion mobilities of CPMP-labelled disaccharides. Among them, [M + 2CPMP + H]
+ was separated with a resolution of 1.484, almost achieving baseline separation. Subsequently, [M + CPMP + Na]+ was used for the relative quantification of lactose and maltose, showing a good linear relationship with R2 > 0.990. Finally, the method was successfully applied to the identification of lactose and maltose in beer and milk. The method is fast, accurate and effective for the identification of disaccharide isomers in complex samples.- Published
- 2024
- Full Text
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21. Conformational Characterization of Peptides and Proteins by 193 nm Ultraviolet Photodissociation in the Collision Cell of a Trapped Ion Mobility Spectrometry-Time-of-Flight Mass Spectrometer.
- Author
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Butalewicz JP, Escobar EE, Wootton CA, Theisen A, Park MA, Seeley EH, and Brodbelt JS
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- Peptides chemistry, Peptides analysis, Mass Spectrometry, Proteins chemistry, Proteins analysis, Animals, Ultraviolet Rays, Ion Mobility Spectrometry, Myoglobin chemistry, Myoglobin analysis, Ubiquitin chemistry, Ubiquitin analysis, Protein Conformation
- Abstract
Ultraviolet photodissociation (UVPD) has been shown to be a versatile ion activation strategy for the characterization of peptides and intact proteins among other classes of biological molecules. Combining the high-performance mass spectrometry (MS/MS) capabilities of UVPD with the high-resolution separation of trapped ion mobility spectrometry (TIMS) presents an opportunity for enhanced structural elucidation of biological molecules. In the present work, we integrate a 193 nm excimer laser in a TIMS-time-of-flight (TIMS-TOF) mass spectrometer for UVPD in the collision cell and use it for the analysis of several mass-mobility-selected species of ubiquitin and myoglobin. The resultant data displayed differences in fragmentation that could be correlated with changes in protein conformation. Additionally, this mobility-resolved UVPD strategy was applied to collision-induced unfolded ions of ubiquitin to follow changes in fragmentation patterns relating to the extent of protein unfolding. This platform and methodology offer new opportunities for exploring how conformational variations are manifested in the fragmentation patterns of gas-phase ions.
- Published
- 2024
- Full Text
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22. Metal Polycation Adduction to Lipids Enables Superior Ion Mobility Separations with Ultrafast Ozone-Induced Dissociation.
- Author
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Shvartsburg AA, Sadowski P, Poad BLJ, and Blanksby SJ
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- Lipids chemistry, Isomerism, Cations chemistry, Metals chemistry, Polyelectrolytes chemistry, Ozone chemistry, Ion Mobility Spectrometry methods
- Abstract
Specific lipid isomers are functionally critical, but their structural rigidity and usually minute geometry differences make separating them harder than other biomolecules. Such separations by ion mobility spectrometry (IMS) were recently enabled by new high-definition methods using dynamic electric fields, but major resolution gains are needed. Another problem of identifying many isomers with no unique fragments in ergodic collision-induced dissociation (CID) was partly addressed by the direct ozone-induced dissociation (OzID) that localizes the double bonds, but a low reaction efficiency has limited the sensitivity, dynamic range, throughput, and compatibility with other tools. Typically lipids are analyzed by MS as singly charged protonated, deprotonated, or ammoniated ions. Here, we explore the differential IMS (FAIMS) separations with OzID for exemplary lipids cationized by polyvalent metals. These multiply charged adducts have much greater FAIMS compensation voltages ( U
C ) than the 1+ ions, with up to 10-fold resolution gain enabling baseline isomer separations even at a moderate resolving power of the SelexION stage. Concomitantly OzID speeds up by many orders of magnitude, producing a high yield of diagnostic fragments already in 1 ms. These capabilities can be ported to the superior high-definition FAIMS and high-pressure OzID systems to take lipidomic analyses to the next level.- Published
- 2024
- Full Text
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23. Streamlining Phenotype Classification and Highlighting Feature Candidates: A Screening Method for Non-Targeted Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS) Data.
- Author
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Chappel JR, Kirkwood-Donelson KI, Dodds JN, Fleming J, Reif DM, and Baker ES
- Subjects
- Chromatography, Liquid methods, Support Vector Machine, Humans, Ion Mobility Spectrometry methods, Mass Spectrometry methods, Phenotype
- Abstract
Nontargeted analysis (NTA) is increasingly utilized for its ability to identify key molecular features beyond known targets in complex samples. NTA is particularly advantageous in exploratory studies aimed at identifying phenotype-associated features or molecules able to classify various sample types. However, implementing NTA involves extensive data analyses and labor-intensive annotations. To address these limitations, we developed a rapid data screening capability compatible with NTA data collected on a liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) platform that allows for sample classification while highlighting potential features of interest. Specifically, this method aggregates the thousands of IMS-MS spectra collected across the LC space for each sample and collapses the LC dimension, resulting in a single summed IMS-MS spectrum for screening. The summed IMS-MS spectra are then analyzed with a bootstrapped Lasso technique to identify key regions or coordinates for phenotype classification via support vector machines. Molecular annotations are then performed by examining the features present in the selected coordinates, highlighting potential molecular candidates. To demonstrate this summed IMS-MS screening approach, we applied it to clinical plasma lipidomic NTA data and exposomic NTA data from water sites with varying contaminant levels. Distinguishing coordinates were observed in both studies, enabling the evaluation of phenotypic molecular annotations and resulting in screening models capable of classifying samples with up to a 25% increase in accuracy compared to models using annotated data.
- Published
- 2024
- Full Text
- View/download PDF
24. Fast and broad-coverage lipidomics enabled by ion mobility-mass spectrometry.
- Author
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Cai Y, Chen X, Ren F, Wang H, Yin Y, and Zhu ZJ
- Subjects
- Humans, Lipids analysis, Lipids blood, Lipid Metabolism, Chromatography, Liquid methods, Lipidomics methods, Ion Mobility Spectrometry methods, Colorectal Neoplasms, Mass Spectrometry methods
- Abstract
Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies.
- Published
- 2024
- Full Text
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25. An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry.
- Author
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Koomen DC, May JC, Mansueto AJ, Graham TR, and McLean JA
- Subjects
- Animals, Mice, Workflow, Mass Spectrometry methods, Isomerism, Chromatography, Liquid methods, Mice, Inbred C57BL, Algorithms, Ion Mobility Spectrometry methods, Lipidomics methods, Lipids chemistry, Lipids analysis
- Abstract
Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power ( R > 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.
p > 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.- Published
- 2024
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26. Identifying and Quantifying Relative Concentrations of Epimers in Mixtures via Cyclic Ion Mobility Mass Spectrometry: Dexamethasone and Betamethasone as a Case Study.
- Author
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Mane SS, Dearden DV, and Lee KW
- Subjects
- Isomerism, Dexamethasone analysis, Dexamethasone chemistry, Betamethasone analysis, Betamethasone chemistry, Ion Mobility Spectrometry methods, Dimerization, Mass Spectrometry methods
- Abstract
Epimers can show different biological activities and different pharmacological behaviors; therefore, their separation and analysis are crucial in the drug development process. Due to their similar chemical and physical properties, separation of epimers is challenging. This study demonstrates the application of cyclic ion mobility-mass spectrometry to separate, identify, and quantify dexamethasone and betamethasone in a binary mixture. Cyclic IMS separation of the isolated protonated dimer resulted in three peaks: dexamethasone homodimer, betamethasone homodimer, and their heterodimer. Besides providing improved separation over the protonated monomer, the presence of a heterodimer peak provides additional confirmation of an isomeric mixture. We identified the dexamethasone and betamethasone homodimer peaks by infusing pure solutions of each epimer and measuring each pure homodimer's arrival time. The measured peak areas indicated that the heterodimer is formed at twice the rate of each homodimer and that dexamethasone and betamethasone contribute equally to the heterodimer signal. Using this observation, we could accurately calculate the relative concentrations of each epimer by adding half of the heterodimer peak area to each homodimer peak area. These findings enable the identification and quantification of dexamethasone and betamethasone based on the arrival time distributions of their protonated dimers. This is the first demonstration of accurate relative quantification of epimers by separating charged dimers in the gas phase.
- Published
- 2024
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27. Identification of Key Volatile Compounds in Tilapia during Air Frying Process by Quantitative Gas Chromatography-Ion Mobility Spectrometry.
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Chen T, Xue Y, Li C, Zhao Y, Huang H, Feng Y, Xiang H, and Chen S
- Subjects
- Animals, Gas Chromatography-Mass Spectrometry, Odorants analysis, Hot Temperature, Air analysis, Volatile Organic Compounds analysis, Volatile Organic Compounds chemistry, Tilapia metabolism, Ion Mobility Spectrometry methods, Cooking
- Abstract
Air frying as a new roasting technology has potential for roasted fish production. In this study, the changes in volatile compounds (VCs) during air frying of tilapia were studied by quantitative gas chromatography-ion mobility spectrometry, followed by the identification of key VCs based on their odor activity value (OAV). There were 34 verified VCs, of which 16 VCs were identified as the key VCs with OAV ≥ 1. Most of the VCs were improved by air frying and peaked at 20 min. During the air frying, the total sulfhydryl content markedly decreased, while the protein carbonyl and MDA content significantly increased, suggesting the enhancement in the oxidation of lipids and proteins. The correlation network among the chemical properties and key VCs was constructed. The change in total sulfhydryl, protein carbonyl, and MDA showed significant correlation with most of the key VCs, especially 2-methyl butanal, ethyl acetate, and propanal. The results indicated that the oxidation of lipids and proteins contributed the most to the flavor improvement in air-fried tilapia. This study provides a crucial reference for the volatile flavor improvement and pre-cooked product development of roasted tilapia.
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- 2024
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28. Top-Down Structural Characterization of Native Ubiquitin Combining Solution-Stable Isotope Labeling, Trapped Ion Mobility Spectrometry, and Tandem Electron Capture Dissociation Mass Spectrometry.
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Jeanne Dit Fouque K, Fernandez-Rojas M, Roque AE, and Fernandez-Lima F
- Subjects
- Deuterium Exchange Measurement, Tandem Mass Spectrometry methods, Solutions, Protein Conformation, Models, Molecular, Amino Acid Sequence, Ubiquitin chemistry, Ion Mobility Spectrometry, Isotope Labeling
- Abstract
Solution-phase hydrogen/deuterium exchange (HDX) coupled to native ion mobility spectrometry mass spectrometry (IMS-MS) can provide complementary structural information about the conformational dynamics of biological molecules. In the present work, the solution-stable isotope labeling (SIL) combined with trapped ion mobility spectrometry (TIMS) in tandem with top-down electron capture dissociation (ECD) is illustrated for the structural characterization of the solution native states of ubiquitin. Four different ubiquitin electrospray solution conditions: (i) single-tip nondeuterated, (ii) theta tip for online SIL HDX, (iii) single-tip SIL-deuterated, and (iv) theta tip for online SIL H/D back exchange (HDbX), were investigated to assess the H/D exchange reactivities of native ubiquitin. The combination of TIMS and ECD in a q-ToF MS instrument allowed for additional inspection of gas-phase HDbX added by top-down fragmentation, revealing the exposed and protected residues with limited scrambling effects (e.g., intramolecular H/D migration). A native charge state distribution (5+ to 7+) and TIMS profiles were observed under the single-tip nondeuterated solution conditions. Mass shift distributions of ∼40, ∼104, and ∼87D were observed when incorporating deuterium for online SIL HDX, SIL HDX, and online SIL HDbX, respectively, while retaining similar conformational states. ECD fragmentation allowed for the localization of the deuterated labeled residues of the peptide fragments, with a sequence coverage of ∼90%, for each of the ubiquitin solution condition. Changes in the TIMS trapping time settings (∼70 to ∼795 ms) were used to determine the H/D back exchange dynamics of native ubiquitin. HDbX-TIMS-q-ECD-MS/MS exhibited H/D back exchanges in the six-residue C-terminal tail as well as around Lys6, Lys11, Lys33, Lys48, and Lys63 residues, indicating that these regions are the most exposed area (less protected hydrogens) of ubiquitin as compared to the rest of the core residues that adopt a compact β-grasp fold (protected hydrogens), which was consistent with the accessible surface area of ubiquitin. The present data highlight for the first time consistency between the solution HDX and gas-phase HDbX-TIMS data for native studies.
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- 2024
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29. Time-Resolved Ion Mobility-Mass Spectrometry Reveals Structural Transitions in the Disassembly of Modular Polyketide Syntheses.
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Zhao C, Slocum ST, Sherman DH, and Ruotolo BT
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- Mass Spectrometry methods, Protein Multimerization, Models, Molecular, Protein Conformation, Ion Mobility Spectrometry methods, Polyketide Synthases chemistry, Polyketide Synthases metabolism, Polyketides chemistry, Polyketides metabolism
- Abstract
The type 1 polyketide synthase (PKS) assembly line uses its modular structure to produce polyketide natural products that form the basis of many pharmaceuticals. Currently, several cryoelectron microscopy (cryo-EM) structures of a multidomain PKS module have been constructed, but much remains to be learned. Here we utilize ion-mobility mass spectrometry (IM-MS) to record size and shape information and detect different conformational states of a 207 kDa didomain dimer comprised of ketosynthase (KS) and acyl transferase (AT), excised from full-length module. Furthermore, gas-phase stability differences between these different conformations are captured by collision induced unfolding (CIU) technology. Additionally, through tracking these forms as a function of time, we elucidate a detailed disassembly pathway for KS-AT dimers for the first time.
- Published
- 2024
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30. Sweat-based stress screening with gas chromatography-ion mobility spectrometry and electronic nose.
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Tungkijanansin N, Sirinara P, Tunvirachaisakul C, Srikam S, Kittiban K, Thongthip S, Kerdcharoen T, Maes M, and Kulsing C
- Subjects
- Humans, Female, Adult, Gas Chromatography-Mass Spectrometry, Stress, Psychological diagnosis, Volatile Organic Compounds analysis, Middle Aged, Sweat chemistry, Electronic Nose, Ion Mobility Spectrometry methods
- Abstract
Background: Diagnosis of stress generally involves uses of questionnaires which can provide biased results. The more reliable approach relies on observation of individual symptoms by psychiatrists which is time consuming and could not be applicable for massive scale screening tests. This research established alternative approaches with gas chromatography-ion mobility spectrometry (GC-IMS) and electronic nose (e-nose) to perform fast stress screening based on fingerprinting of highly volatile compounds in headspaces of sweat. The investigated samples were obtained from 154 female nurse volunteers who also provided the data of questionnaire-based mental health scores with the high stress cases confirmed by psychiatrists., Results: The interviews by psychiatrists revealed 14 volunteers with high stress. Their axillary sweat samples and that from 32 nurses with low/moderate stress (controls) were collected onto cotton rods and analysed with GC-IMS. The possible marker peaks were selected based on the accuracy data. They were tentatively identified as ammonia, diethyl ether, methanol, octane, pentane, acetone and dimethylamine which could involve different endogenous mechanisms or the relationships with the local microbiomes. The data were further analysed using partial least squares discriminant analysis with the receiver operating characteristic curves showing the optimum accuracy, sensitivity and selectivity of 87%, 86% and 88%, respectively. Providing that the samples were obtained from the nurses without deodorant uses, the high stress cases could be screened using e-nose sensors with the accuracy of 89%. The sensor responses could be correlated with the marker peak area data in GC-IMS with the coefficients ranging from -0.70 to 0.80., Significance: This represents the first investigation of highly volatile compound markers in sweat for high stress screening. The established methods were simple, reliable, rapid and non-invasive, which could be further adapted into the portable platform of e-nose sensors with the practical application to perform the screening tests for nurses in Phra Nakorn Si Ayutthaya hospital, Thailand., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Chadin Kulsing and Nuttanee Tungkijanansin report equipment, or supplies was provided by Second Century Fund (C2F), Chulalongkorn University. The 90th anniversary of Chulalongkorn University fund (Ratchadaphiseksomphot Endowment Fund) and Researcher assistant fellowship of Chulalongkorn University. Chadin Kulsing reports a relationship with Second Century Fund (C2F), Chulalongkorn University. That includes: funding grants., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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31. Hyphenation of supercritical fluid chromatography and trapped ion mobility-mass spectrometry for quantitative lipidomics.
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Scholz J, Rudt E, Gremme A, Gaßmöller Née Wienken CM, Bornhorst J, and Hayen H
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- Animals, Mass Spectrometry methods, Chromatography, Supercritical Fluid methods, Caenorhabditis elegans metabolism, Caenorhabditis elegans chemistry, Ion Mobility Spectrometry methods, Lipidomics methods, Lipids analysis, Lipids chemistry
- Abstract
Background: Lipidomics studies require rapid separations with accurate and reliable quantification results to further elucidate the role of lipids in biological processes and their biological functions. Supercritical fluid chromatography (SFC), in particular, can provide this rapid and high-resolution separation. The combination with trapped ion mobility spectrometry (TIMS) has not yet been applied, although the post-ionization separation method in combination with liquid chromatography or imaging techniques has already proven itself in resolving isomeric and isobaric lipids and preventing false identifications. However, a multidimensional separation method should not only allow confident identification but also provide quantitative results to substantiate studies with absolute concentrations., Results: A SFC method was developed and the hyphenation of SFC and TIMS was further explored towards the separation of different isobaric overlaps. Furthermore, lipid identification was performed using mass spectrometry (MS) and parallel accumulation serial fragmentation (PASEF) MS/MS experiments in addition to retention time and collision cross section (CCS). Quantification was further investigated with short TIMS ramps and performed based on the ion mobility signal of lipids, since TIMS increases the sensitivity by noise filtering. The final method was, as an exemplary study, applied to investigate the function of different ceramide synthases (CerS) in the nematode and model organism Caenorhabditis elegans (C. elegans). Loss of three known CerS hyl-1, hyl-2 and lagr-1 demonstrated different influences on and alterations in the sphingolipidome., Significance: This method describes for the first time the combination of SFC and TIMS-MS/MS, which enables a fast and sensitive quantification of lipids. The results of the application to C. elegans samples prove the functionality of the method and support research on the metabolism of sphingolipids in nematodes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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32. Characterization of spironolactone and metabolites derivatized using Girard's reagent P using mass spectrometry and ion mobility spectrometry.
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Jones SM, Kirkwood-Donelson KI, Alexander GM, Perera L, Dudek SM, and Jarmusch AK
- Subjects
- Chromatography, High Pressure Liquid methods, Animals, Mice, Male, Spironolactone chemistry, Spironolactone blood, Spironolactone metabolism, Tandem Mass Spectrometry methods, Spectrometry, Mass, Electrospray Ionization methods, Ion Mobility Spectrometry methods
- Abstract
Rationale: Spironolactone is a steroidal drug prescribed for a variety of medical conditions and is extensively metabolized quickly after administration. Measurement of spironolactone and its metabolites remains challenging using mass spectrometry (MS) due to in-source fragmentation and relatively poor ionization using electrospray ionization. Therefore, improved methods of measurements are needed, particularly in the case of small sample volumes., Methods: Girard's reagent P (GP) derivatization of spironolactone was employed to improve response and provide an MS-based solution to the measurement of spironolactone and its metabolites. We performed ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) and ion mobility spectrometry (IMS)-high-resolution mass spectrometry (HRMS) to fully characterize the GP derivatization products. Analytes were studied in positive ionization mode, and MS/MS was performed using nonresonance and resonance excitation collision-induced dissociation., Results: We observed the successful GP derivatization of spironolactone and its metabolites using authentic chemical standards. A signal enhancement of 1-2 orders of magnitude was observed for GP-derivatized versions of spironolactone and its metabolites. Further, GP derivatization eliminated in-source fragmentation. Finally, we performed GP derivatization and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) in a small volume of murine serum (20 μL) from spironolactone-treated and control animals and observed multiple spironolactone metabolites only in the spironolactone-treated group., Conclusions: GP derivatization was proven to have advantageous mass spectral performance (e.g., limiting in-source fragmentation, enhancing signals, and eliminating isobaric analytes) for spironolactone and its metabolites. This work and the detailed characterization using ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) and IMS serve as the foundation for future developments in reaction optimization and/or quantitative assay development., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)
- Published
- 2024
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33. Cyclic Ion Mobility of Isomeric New Psychoactive Substances Employing Characteristic Arrival Time Distribution Profiles and Adduct Separation.
- Author
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Nytka M, Wan J, Tureček F, and Lemr K
- Subjects
- Isomerism, Spectrometry, Mass, Electrospray Ionization methods, Lithium chemistry, Psychotropic Drugs chemistry, Psychotropic Drugs analysis, Ion Mobility Spectrometry methods
- Abstract
Analysis of new psychoactive substances (NPS), which is essential for toxicological and forensic reasons, can be made complicated by the presence of isomers. Ion mobility has been used as a standalone technique or coupled to mass spectrometry to detect and identify NPS. However, isomer separation has so far chiefly relied on chromatography. Here we report on the determination of isomeric ratios using cyclic ion mobility-mass spectrometry without any chromatographic separation. Isomers were distinguished by mobility separation of lithium adducts. Alternatively, we used arrival time distribution (ATD) profiles that were characteristic of individual isomers and were acquired for protonated molecules or fragment ions. Both approaches provided comparable results. Calculations were used to determine the structures and collision cross sections of both protonated and lithiated isomers that accurately characterized their ion mobility properties. The applicability of ATD profiles to isomer differentiation was demonstrated using direct infusion and flow injection analysis with electrospray of solutions, as well as desorption electrospray of solid samples. Data processing was performed by applying multiple linear regression to the ATD profiles. Using the proposed ATD profile-based approach, the relationships between the determined and given content of isomers showed good linearity with coefficients of determination typically greater than 0.99. Flow injection analysis using an autosampler allowed us to rapidly determine isomeric ratios in a sample containing two isomeric pairs with a minor isomer of 10% (determined 9.3% of 3-MMC and 11.0% of 3-FMC in a mixture with buphedrone and 4-FMC). The proposed approach is not only useful for NPS, but also may be applicable to small isomeric molecules analyzed by ion mobility when complete separation of isomers is not achieved.
- Published
- 2024
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34. Direct Enantiomer Differentiation of Drugs and Drug-Like Compounds via Noncovalent Copper-Amino Acid Complexation and Ion Mobility-Mass Spectrometry.
- Author
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Blakley BK, Zlibut E, Gupta RM, May JC, and McLean JA
- Subjects
- Stereoisomerism, Mass Spectrometry methods, Pharmaceutical Preparations chemistry, Pharmaceutical Preparations analysis, Coordination Complexes chemistry, Molecular Structure, Copper chemistry, Amino Acids chemistry, Amino Acids analysis, Ion Mobility Spectrometry methods
- Abstract
Drug enantiomers can possess vastly different pharmacological properties, yet they are identical in their chemical composition and structural connectivity. Thus, resolving enantiomers poses a great challenge in the field of separation science. Enantiomer separations necessitate interaction of the analyte with a chiral environment─in mass spectrometry-based analysis, a common approach is through a three-point interaction with a chiral selector commonly introduced during sample preparation. In select cases, the structural difference imparted through noncovalent complexation results in enantiomer-specific structural differences, facilitating measurement using a structurally selective analytical technique such as ion mobility-mass spectrometry (IM-MS). In this work, we investigate the direct IM-MS differentiation of chiral drug compounds using mononuclear copper complexes incorporating an amino acid chiral selector. A panel of 20 chiral drugs and drug-like compounds were investigated for separation, and four l-amino acids (l-histidine, l-tryptophan, l-proline, and l-tyrosine) were evaluated as chiral selectors (CS) to provide the chiral environment necessary for differentiation. Enantiomer differentiation was achieved for four chiral molecule pairs ( R / S -thalidomide, R / S -baclofen, R / S -metoprolol, and d/l-panthenol) with two-peak resolution ( R
p-p ) values ranging from 0.7 (>10% valley) to 1.5 (baseline separation). Calibration curves relating IM peak areas to enantiomeric concentrations enabled enantiomeric excess quantitation of racemic thalidomide and metoprolol with residuals of 5.7 and 2.5%, respectively. Theoretical models suggest that CuII and l-histidine complexation around the analyte chiral center is important for gas-phase stereoselectivity. This study demonstrates the potential of combining enantioselective noncovalent copper complexation with structurally selective IM-MS for differentiating chiral drugs and drug-like compounds.- Published
- 2024
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35. Towards the Development of an In-Process Quality Monitoring System for Polyethylene Recyclates by Pyrolysis Gas Chromatography Ion Mobility Spectrometry
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Ahrens, André, Shamsuyeva, Madina, Endres, Hans-Josef, and Zimmermann, Stefan
- Published
- 2024
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36. Investigating direct current potentials that affect native protein conformation during trapped ion mobility spectrometry-mass spectrometry.
- Author
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Voeten RLC, Majeed HA, Bos TS, Somsen GW, and Haselberg R
- Subjects
- Animals, Cattle, Mass Spectrometry methods, Protein Conformation, Ions, Ion Mobility Spectrometry methods, Proteins chemistry
- Abstract
Trapped ion mobility spectrometry-time-of-flight mass spectrometry (TIMS-TOFMS) has emerged as a tool to study protein conformational states. In TIMS, gas-phase ions are guided across the IM stages by applying direct current (DC) potentials (D1-6), which, however, might induce changes in protein structures through collisional activation. To define conditions for native protein analysis, we evaluated the influence of these DC potentials using the metalloenzyme bovine carbonic anhydrase (BCA) as primary test compound. The variation of DC potentials did not change BCA-ion charge and heme content but affected (relative) charge-state intensities and adduct retention. Constructed extracted-ion mobilograms and corresponding collisional cross-section (CCS) profiles gave useful insights in (alterations of) protein conformational state. For BCA, the D3 and D6 potential (which are applied between the deflection transfer and funnel 1 [F1] and the accumulation exit and the start of the ramp, respectively) had most profound effects, showing multimodal CCS distributions at higher potentials indicating gradual unfolding. The other DC potentials only marginally altered the CCS profiles of BCA. To allow for more general conclusions, five additional proteins of diverse molecular weight and conformational stability were analyzed, and for the main protein charge states, CCS profiles were constructed. Principal component analysis (PCA) of the obtained data showed that D1 and D3 exhibit the highest degree of correlation with the ratio of folded and unfolded protein (F/U) as extracted from the mobilograms obtained per set D potential. The correlation of D6 with F/U and protein charge were similar, and D2, D4, and D5 showed an inverse correlation with F/U but were correlated with protein charge. Although DC boundary values for induced conformational changes appeared protein dependent, a set of DC values could be determined, which assured native analysis of most proteins., (© 2024 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons Ltd.)
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- 2024
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37. Impact of Ion Mobility on Electron Density and Temperature in Hypersonic Flows
- Author
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Fuentes, Felipe Martin Rodriguez and Parent, Bernard
- Subjects
Physics - Plasma Physics - Abstract
This study provides the first comprehensive analysis of how ion mobility affects electron density and temperature in hypersonic flows. We compare two ion mobility models: one derived from Gupta-Yos cross-sections, and the other from swarm drift velocity experiments. The ion mobility model significantly alters the plasma density around a hypersonic waverider, with increases of more than twofold observed at low dynamic pressures and high Mach numbers. This is partly due to electron loss through surface catalysis, which depends on ambipolar diffusion scaling with ion mobility. We also derive novel scaling laws that highlight the strong dependence of electron cooling on ion mobility both within the quasi-neutral regions and the non-neutral plasma sheaths. Electron cooling influences the electron temperature across the plasma, leading to a previously unrecognized impact of ion mobility on plasma bulk temperature. This in turn affects plasma density via electron-ion recombination rates which are temperature-dependent. Accurately modeling ion mobility is critical for predicting hypersonic plasma behavior, with important implications for optimizing magnetohydrodynamic technologies and mitigating or exploiting plasma-induced interference with electromagnetic waves., Comment: 31 pages, 11 figures, 5 tables
- Published
- 2024
38. Detecting Trace Amounts of Peroxides and Ammonium Nitrate in Fingerprints by Ion Mobility Spectrometry
- Author
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Buryakov, T. I. and Buryakov, I. A.
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- 2024
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39. Mildew Detection for Stored Wheat using Gas Chromatography–Ion Mobility Spectrometry and Broad Learning Network
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Fu, Maixia and Lian, Feiyu
- Published
- 2024
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40. Separation of mycolic acid isomers by cyclic ion mobility-mass spectrometry.
- Author
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de Las Heras Prieto H, Cole LM, Forbes S, Palmer M, and Schwartz-Narbonne R
- Subjects
- Isomerism, Mycolic Acids chemistry, Mycolic Acids analysis, Ion Mobility Spectrometry methods, Mass Spectrometry methods, Mycobacterium bovis chemistry
- Abstract
Rationale: Mycobacterial species contain high concentrations of mycolic acids in their cell wall. Mycobacteria can pose a threat to both human health and the environment. Mass spectrometry lipidomic characterization can identify bacterial species and suggest targets for microbiological interventions. Due to the complex structures of mycolic acids and the possibility of isobaric isomers, multiple levels of separation are required for complete characterization. In this study, cyclic ion mobility (cIM) mass spectrometry (MS) was used for the analysis, separation and fragmentation of mycolic acids isomers from the bacterial species Gordonia amarae and Mycobacterium bovis., Methods: Mycolic acid isomers were interrogated from cultured G. amarae biomass and commercially available M. bovis mycolic acid extracts. These were infused into a cIM-enabled quadrupole time-of-flight MS. Ions of interest were non-simultaneously selected with the quadrupole and passed around the cyclic ion mobility device multiple times. Fragment ion analysis was then performed for the resolved isomers of the quadrupole-selected ions., Results: Repeated passes of the cIM device successfully resolved otherwise overlapping MA isomers, allowing isomer isolation and producing an ion-specific post-mobility fragmentation spectrum without isomeric interference., Conclusions: Mycolic acids (MA) isomers from G. amarae and M. bovis were resolved, resulting in a high mobility resolution and low interference fragmentation analysis. These revealed varying patterns of MA isomers in the two species: G. amarae's most abundant ion of each set of MA has 1-2 conformations, while the MA + 2 m/z the most abundant ion of each set has 3-6 conformations. These were resolved after 70 passes of the cyclic device. M. bovis' most abundant ion of each keto-MA set has 2 conformations, while the keto-MA + 2 m/z has 1-2 conformations. These were resolved after 75 passes., (© 2024 The Author(s). Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)
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- 2024
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41. Computational tools and algorithms for ion mobility spectrometry-mass spectrometry.
- Author
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Ross DH, Bhotika H, Zheng X, Smith RD, Burnum-Johnson KE, and Bilbao A
- Subjects
- Proteomics methods, Metabolomics methods, Humans, Ion Mobility Spectrometry methods, Algorithms, Software, Mass Spectrometry methods
- Abstract
Ion mobility spectrometry-mass spectrometry (IMS-MS or IM-MS) is a powerful analytical technique that combines the gas-phase separation capabilities of IM with the identification and quantification capabilities of MS. IM-MS can differentiate molecules with indistinguishable masses but different structures (e.g., isomers, isobars, molecular classes, and contaminant ions). The importance of this analytical technique is reflected by a staged increase in the number of applications for molecular characterization across a variety of fields, from different MS-based omics (proteomics, metabolomics, lipidomics, etc.) to the structural characterization of glycans, organic matter, proteins, and macromolecular complexes. With the increasing application of IM-MS there is a pressing need for effective and accessible computational tools. This article presents an overview of the most recent free and open-source software tools specifically tailored for the analysis and interpretation of data derived from IM-MS instrumentation. This review enumerates these tools and outlines their main algorithmic approaches, while highlighting representative applications across different fields. Finally, a discussion of current limitations and expectable improvements is presented., (© 2024 Battelle Memorial Institute. PROTEOMICS published by Wiley‐VCH GmbH.)
- Published
- 2024
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42. Innovative direct introduction-ion mobility-mass spectrometry (DI-IM-MS) approach for fast and robust isomer-specific quantification in a complex matrix: Application to 2'-fucosyllactose (2'-FL) in breast milk.
- Author
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Rathahao-Paris E, Abdoun S, Paris A, Guillon B, Venot E, Fenaille F, Adel-Patient K, and Alves S
- Subjects
- Humans, Isomerism, Female, Mass Spectrometry methods, Milk, Human chemistry, Trisaccharides analysis, Trisaccharides chemistry, Oligosaccharides analysis, Oligosaccharides chemistry, Ion Mobility Spectrometry methods
- Abstract
Identification and specific quantification of isomers in a complex biological matrix by mass spectrometry alone is not an easy task due to their identical chemical formula and therefore their same mass-to-charge ratio (m/z). Here, the potential of direct introduction combined with ion mobility-mass spectrometry (DI-IM-MS) for rapid quantification of isomers as human milk oligosaccharides (HMOs) was investigated. Differences in HMO profiles between various analyzed breast milk samples were highlighted using the single ion mobility monitoring (SIM
2 ) acquisition for high ion mobility resolution detection. Furthermore, the Se+ (secretor) or Se- (non-secretor) phenotype could be assigned to breast milk samples studied based on their HMO contents, especially on the response of 2'-fucosyllactose (2'-FL) and lacto-N-fucopentaose I (LNFP I). The possibility of quantifying a specific isomer in breast milk by DI-IM-MS was also investigated. The standard addition method allowed the determination of the 2'-FL despite the presence of other oligosaccharides, including 3-fucosyllactose (3-FL) isomer in breast milk. This proof-of-concept study demonstrated the high potential of such an approach for the rapid and convenient quantification of isomers in complex mixtures., (© 2024 John Wiley & Sons, Ltd.)- Published
- 2024
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43. A study on the determination of the metabolites of 2,4,6-Trinitrotoluene using a dual-drift tube ion mobility spectrometer.
- Author
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Zhang X, Luo Y, Xia L, Song Y, Li W, Kong L, Liu Y, Shen C, Huang C, and Chu Y
- Subjects
- Humans, Limit of Detection, Aniline Compounds, Trinitrotoluene analysis, Trinitrotoluene urine, Ion Mobility Spectrometry methods
- Abstract
2,4,6-Trinitrotoluene (TNT) and its four metabolites, namely 2-ADNT, 4-ADNT, 2,4-DANT, and 2,6-DANT, are highly toxic substances. These metabolites also serve as biomarkers for assessing the health of individuals exposed to TNT. In this study, a homemade DDT-IMS apparatus was utilized to detect these metabolites. Under negative detection mode, the drift times of 2-ADNT and 4-ADNT showed subtle shifts within a drift tube temperature range of 100 °C-120 °C, aiding in their differentiation. In positive detection mode for 2,4-DANT and 2,6-DANT, significant variations were observed in both the number and drift time of their positive product ions across a drift tube temperature range of 80 °C-120 °C. Consequently, optimal analytical performance for these metabolites was achieved at approximately 100 °C. Evaluation of the instrumental response during the measurement of the four metabolites in both positive and negative modes revealed that negative detection mode offered greater advantages of detecting these compounds. The working ranges for measuring the four metabolites spanned two orders of magnitude, with detection limits for each metabolite nearly below 1 ng. Notably, clear identification of the signals for these metabolites was achieved even when samples were mixed in urine, highlighting the ability of the DDT-IMS in detecting TNT metabolites. The developed DDT-IMS detection method has significant potential for enhancing environmental risk assessment and biological hazard evaluation, particularly in relation to human exposure to TNT., Competing Interests: Declaration of competing interest Neither the entire manuscript nor any part of its content has been published or has been accepted elsewhere and this manuscript has not been submitted to any other journal. No portion of the text has been copied from other material in the literature. All of the authors in this manuscript have read and approved the final version submitted, and declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2025
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- View/download PDF
44. Analytical characterization of anthocyanins using trapped ion mobility spectrometry-quadrupole time-of-flight tandem mass spectrometry.
- Author
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Schnitker FA, Steingass CB, and Schweiggert R
- Subjects
- Chromatography, High Pressure Liquid, Fruit and Vegetable Juices analysis, Fruit chemistry, Plant Extracts chemistry, Blueberry Plants chemistry, Anthocyanins chemistry, Anthocyanins analysis, Tandem Mass Spectrometry, Ion Mobility Spectrometry methods, Vitis chemistry
- Abstract
Anthocyanin profiles of juices from blueberry (Vaccinium myrtillus L.) and different grape varieties (Vitis labrusca L. cv. Concord, Vitis vinifera L. cvs. Accent, Dunkelfelder, Dakapo, and GM 674-1) were characterized by ultra-high performance liquid chromatography (UHPLC) coupled to trapped ion mobility spectrometry-quadrupole time-of-flight tandem mass spectrometry (TIMS-QTOF-MS/MS). Ion mobility and collision cross section (CCS) values of over 50 structurally related anthocyanins based on delphinidin, cyanidin, petunidin, peonidin, and malvidin were determined. Relations between molecular mass, mobility values, and specific structural features were revealed. The mass-to-charge (m/z) ratio of the molecular ions (M
+ ) was found to be the major factor influencing anthocyanin ion mobilities, but structural characteristics also contributed to their variability. We were able to differentiate positional and geometrical isomers and certain epimers by their respective mobility values. For instance, whereas 3-O-hexosides (i.e., 3-O-glucosides and 3-O-galactosides) were separated by TIMS, epimers of 3-O-pentosides assessed could not be distinguished., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
- Full Text
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45. Differentiation of Cis/trans-geometrical isomers in long-chain unsaturated fatty acids based on ion mobility and theoretical calculations.
- Author
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He S, Shi L, Zheng ZW, Wu F, and Ding CF
- Subjects
- Isomerism, Mass Spectrometry, Ion Mobility Spectrometry methods, Fatty Acids, Unsaturated chemistry
- Abstract
In recent years, fatty acids containing conjugated CCs have attracted extensive research attention due to their biological activities against human diseases. However, their differentiation is challenging. This study developed a comprehensive analytical solution to accurately differentiate cis/trans-fatty acid isomers using ion mobility mass spectrometry (IM-MS) and theoretical calculations. Cis/trans-fatty acids were mobility-differentiated via simple complexation with 1,5,9-triazacyclododecane (9C3N) or 1,4,8,11-tetraazacyclotetradecane (10C4N) and metal ions, obtaining baseline separation with a peak-to-peak resolution of 0.35-0.92. Moreover, the conformation of the complexes was optimized theoretically, revealing different binding modes between the cis/trans-fatty acid-9C3N/10C4N-metal ion systems, yielding in-depth structural data on the complexes and elucidating the principles of mobility separation. Furthermore, the proposed method was assessed in terms of quantification, accuracy, and precision repeatability. Finally, the method was applied to analyze oil samples. Given its simplicity, speed, and lack of chemical derivatization or chromatographic separation, this technique has potential applications in food analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
46. VOC-based detection of prostate cancer using an electronic nose and ion mobility spectrometry: A novel urine-based approach.
- Author
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Heers H, Chwilka O, Huber J, Vogelmeier C, Koczulla AR, Baumbach JI, and Boeselt T
- Subjects
- Humans, Male, Aged, Middle Aged, Pilot Projects, Sensitivity and Specificity, Aged, 80 and over, Electronic Nose, Volatile Organic Compounds urine, Volatile Organic Compounds analysis, Prostatic Neoplasms urine, Prostatic Neoplasms diagnosis, Ion Mobility Spectrometry methods
- Abstract
Background: Many diseases leave behind specific metabolites which can be detected from breath and urine as volatile organic compounds (VOC). Our group previously described VOC-based methods for the detection of bladder cancer and urinary tract infections. This study investigated whether prostate cancer can be diagnosed from VOCs in urine headspace., Methods: For this pilot study, mid-stream urine samples were collected from 56 patients with histologically confirmed prostate cancer. A control group was formed with 53 healthy male volunteers matched for age who had recently undergone a negative screening by prostate-specific antigen (PSA) and digital rectal exam. Headspace measurements were performed with the electronic nose Cyranose 320
TM . Statistical comparison was performed using principal component analysis, calculating Mahalanobis distance, and linear discriminant analysis. Further measurements were carried out with ion mobility spectrometry (IMS) to compare detection accuracy and to identify potential individual analytes. Bonferroni correction was applied for multiple testing., Results: The electronic nose yielded a sensitivity of 77% and specificity of 62%. Mahalanobis distance was 0.964, which is indicative of limited group separation. IMS identified a total of 38 individual analytical peaks, two of which showed significant differences between groups (p < 0.05). To discriminate between tumor and controls, a decision tree with nine steps was generated. This model led to a sensitivity of 98% and specificity of 100%., Conclusions: VOC-based detection of prostate cancer seems feasible in principle. While the first results with an electronic nose show some limitations, the approach can compete with other urine-based marker systems. However, it seems less reliable than PSA testing. IMS is more accurate than the electronic nose with promising sensitivity and specificity, which warrants further research. The individual relevant metabolites identified by IMS should further be characterized using gas chromatography/mass spectrometry to facilitate potential targeted rapid testing., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)- Published
- 2024
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47. A hyper-fast gas chromatograph coupled to an ion mobility spectrometer with high repetition rate and flow-optimized ion source to resolve the short chromatographic peaks.
- Author
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Nitschke A, Hitzemann M, Winkelholz J, Kirk AT, Lippmann M, Thoben C, Wittwer JA, and Zimmermann S
- Subjects
- Chromatography, Gas methods, Chromatography, Gas instrumentation, Equipment Design, Ion Mobility Spectrometry methods
- Abstract
By combining the high selectivity of a gas chromatograph (GC) with the high sensitivity and decent selectivity of an ion mobility spectrometer (IMS), GC-IMS have become increasingly popular in many applications. However, most GC suffer from long analysis times. In contrast, an hyper-fast GC allows for extremely fast analysis in the tens of seconds while reaching comparably high resolution. In turn, coupling such hyper-fast GC with IMS requires sufficiently high repetition rate of recording full IMS spectra to resolve the short GC peaks. Therefore, we present a drift tube IMS with 100 Hz repetition rate. Key is a small effective detector volume combined with short drift length. Therefore, the ion source of the IMS combines a small reaction region with an extended field-switching ion shutter and optimized gas flows. To resolve even the shortest GC peaks with a full width at half maximum of 100 ms, a short drift length of just 41 mm was used, achieving a measurement time of 10 ms per spectrum and hence ten data points across the shortest GC peak. To avoid condensation of the sample, the entire IMS was heated isothermally to 120 °C. Despite short drift times and high temperatures, the IMS still reaches high resolving power of R
p = 60. The hyper-fast GC-IMS reaches low detection limits in the low ppbV range. For demonstration, ketone mixes and three different hop varieties were analyzed in <30 s., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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48. Letter to the editor for the article "Pilot study for bladder cancer detection with volatile organic compounds using ion mobility spectrometry: a novel urine-based approach".
- Author
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Song Y and Xu T
- Subjects
- Humans, Pilot Projects, Urinary Bladder Neoplasms urine, Urinary Bladder Neoplasms diagnosis, Volatile Organic Compounds urine, Ion Mobility Spectrometry methods
- Published
- 2024
- Full Text
- View/download PDF
49. Elucidating the Gas-Phase Behavior of Nitazene Analog Protomers Using Structures for Lossless Ion Manipulations Ion Mobility-Orbitrap Mass Spectrometry.
- Author
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Hollerbach AL, Lin VS, Ibrahim YM, Ewing RG, Metz TO, and Rodda KE
- Subjects
- Analgesics, Opioid chemistry, Analgesics, Opioid analysis, Tandem Mass Spectrometry methods, Spectrometry, Mass, Electrospray Ionization methods, Benzimidazoles chemistry, Benzimidazoles analysis, Gases chemistry, Nitro Compounds chemistry, Nitro Compounds analysis, Ions chemistry, Ion Mobility Spectrometry methods
- Abstract
2-Benzylbenzimidazoles, or "nitazenes", are a class of novel synthetic opioids (NSOs) that are increasingly being detected alongside fentanyl analogs and other opioids in drug overdose cases. Nitazenes can be 20× more potent than fentanyl but are not routinely tested for during postmortem or clinical toxicology drug screens; thus, their prevalence in drug overdose cases may be under-reported. Traditional analytical workflows utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) often require additional confirmation with authentic reference standards to identify a novel nitazene. However, additional analytical measurements with ion mobility spectrometry (IMS) may provide a path toward reference-free identification, which would greatly accelerate NSO identification rates in toxicology laboratories. Presented here are the first IMS and collision cross section (CCS) measurements on a set of fourteen nitazene analogs using a structures for lossless ion manipulations (SLIM)-orbitrap MS. All nitazenes exhibited two high intensity baseline-separated IMS distributions, which fentanyls and other drug and druglike compounds also exhibit. Incorporating water into the electrospray ionization (ESI) solution caused the intensities of the higher mobility IMS distributions to increase and the intensities of the lower mobility IMS distributions to decrease. Nitazenes lacking a nitro group at the R1 position exhibited the greatest shifts in signal intensities due to water. Furthermore, IMS-MS/MS experiments showed that the higher mobility IMS distributions of all nitazenes possessing a triethylamine group produced fragment ions with m / z 72, 100, and other low intensity fragments while the lower mobility IMS distributions only produced fragment ions with m / z 72 and 100. The IMS, solvent, and fragmentation studies provide experimental evidence that nitazenes potentially exhibit three gas-phase protomers. The cyclic IMS capability of SLIM was also employed to partially resolve four sets of structurally similar nitazene isomers (e.g., protonitazene/isotonitazene, butonitazene/isobutonitazene/secbutonitazene), showcasing the potential of using high-resolution IMS separations in MS-based workflows for reference-free identification of emerging nitazenes and other NSOs.
- Published
- 2024
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50. Hyphenation of Liquid Chromatography and Trapped Ion Mobility - Mass Spectrometry for Characterization of Isomeric Phosphatidylethanolamines with Focus on N -Acylated Species.
- Author
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Rudt E, Schneider S, and Hayen H
- Subjects
- Humans, Isomerism, Chromatography, Liquid methods, Acylation, Hydrophobic and Hydrophilic Interactions, Phosphatidylethanolamines chemistry, Phosphatidylethanolamines analysis, Tandem Mass Spectrometry methods, Ion Mobility Spectrometry methods
- Abstract
In prior research, hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) has demonstrated applicability for characterizing regioisomers in lipidomics studies, including phosphatidylglycerols (PG) and bis(monoacyl)glycerophosphates (BMP). However, there are other lipid regioisomers, such as phosphatidylethanolamines (PE) and lyso- N -acyl-PE (LNAPE), that have not been studied as extensively. Therefore, hyphenated mass spectrometric methods are needed to investigate PE and LNAPE regioisomers individually. The asymmetric structure of LNAPE favors isomeric species, which can result in coelution and chimeric MS/MS spectra. One way to address the challenge of chimeric MS/MS spectra is through mobility-resolved fragmentation using trapped ion mobility spectrometry (TIMS). Therefore, we developed a multidimensional HILIC-TIMS-MS/MS approach for the structural characterization of isomeric phosphatidylethanolamines in both negative and positive ionization modes. The study revealed the complementary fragmentation pattern and ion mobility behavior of LNAPE in both ionization modes, which was confirmed by a self-synthesized LNAPE standard. With this knowledge, a distinction of regioisomeric PE and LNAPE was achieved in human plasma samples. Furthermore, regioisomeric LNAPE species containing at least one unsaturated fatty acid were noted to exhibit a change in collision cross-section in positive ionization mode, leading to a lipid characterization with respect to fatty acyl positional level. Similar mobility behavior was also observed for the biological LNAPE precursor N -acyl-PE (NAPE). Application of this approach to plasma and cereal samples demonstrated its effectiveness in regioisomeric LNAPE and NAPE species' elucidation.
- Published
- 2024
- Full Text
- View/download PDF
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