International Journal of Molecular Sciences

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1744 KiB

Open AccessArticle

Fourier Transform Mass Spectrometry and Nuclear Magnetic Resonance Analysis for the Rapid and Accurate Characterization of Hexacosanoylceramide

by Charles W. Ross, William J. Simonsick, Michael J. Bogusky, Recep W. Celikay, James P. Guare and Randall C. Newton

Int. J. Mol. Sci. 2016, 17(7), 1024; https://doi.org/10.3390/ijms17071024 - 28 Jun 2016

Cited by 1 | Viewed by 5961

Abstract

Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential [...] Read more.

Ceramides are a central unit of all sphingolipids which have been identified as sites of biological recognition on cellular membranes mediating cell growth and differentiation. Several glycosphingolipids have been isolated, displaying immunomodulatory and anti-tumor activities. These molecules have generated considerable interest as potential vaccine adjuvants in humans. Accurate analyses of these and related sphingosine analogues are important for the characterization of structure, biological function, and metabolism. We report the complementary use of direct laser desorption ionization (DLDI), sheath flow electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and high-field nuclear magnetic resonance (NMR) analysis for the rapid, accurate identification of hexacosanoylceramide and starting materials. DLDI does not require stringent sample preparation and yields representative ions. Sheath-flow ESI yields ions of the product and byproducts and was significantly better than monospray ESI due to improved compound solubility. Negative ion sheath flow ESI provided data of starting materials and products all in one acquisition as hexacosanoic acid does not ionize efficiently when ceramides are present. NMR provided characterization of these lipid molecules complementing the results obtained from MS analyses. NMR data was able to differentiate straight chain versus branched chain alkyl groups not easily obtained from mass spectrometry. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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1253 KiB

Open AccessArticle

The Role of Ultrahigh Resolution Fourier Transform Mass Spectrometry (FT-MS) in Astrobiology-Related Research: Analysis of Meteorites and Tholins

by Árpád Somogyi, Roland Thissen, Francois-Régis Orthous-Daunay and Véronique Vuitton

Int. J. Mol. Sci. 2016, 17(4), 439; https://doi.org/10.3390/ijms17040439 - 24 Mar 2016

Cited by 18 | Viewed by 6819

Abstract

It is an important but also a challenging analytical problem to understand the chemical composition and structure of prebiotic organic matter that is present in extraterrestrial materials. Its formation, evolution and content in the building blocks (“seeds”) for more complex molecules, such as [...] Read more.

It is an important but also a challenging analytical problem to understand the chemical composition and structure of prebiotic organic matter that is present in extraterrestrial materials. Its formation, evolution and content in the building blocks (“seeds”) for more complex molecules, such as proteins and DNA, are key questions in the field of exobiology. Ultrahigh resolution mass spectrometry is one of the best analytical techniques that can be applied because it provides reliable information on the chemical composition and structure of individual components of complex organic mixtures. Prebiotic organic material is delivered to Earth by meteorites or generated in laboratories in simulation (model) experiments that mimic space or atmospheric conditions. Recent representative examples for ultrahigh resolution mass spectrometry studies using Fourier-transform (FT) mass spectrometers such as Orbitrap and ion cyclotron resonance (ICR) mass spectrometers are shown and discussed in the present article, including: (i) the analysis of organic matter of meteorites; (ii) modeling atmospheric processes in ICR cells; and (iii) the structural analysis of laboratory made tholins that might be present in the atmosphere and surface of Saturn’s largest moon, Titan. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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1416 KiB

Open AccessArticle

Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry

by Laszlo Prokai and Stanley M. Stevens

Int. J. Mol. Sci. 2016, 17(1), 116; https://doi.org/10.3390/ijms17010116 - 16 Jan 2016

Cited by 7 | Viewed by 6691

Abstract

Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance [...] Read more.

Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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3738 KiB

Open AccessArticle

Selective Analysis of Sulfur-Containing Species in a Heavy Crude Oil by Deuterium Labeling Reactions and Ultrahigh Resolution Mass Spectrometry

by Xuxiao Wang and Wolfgang Schrader

Int. J. Mol. Sci. 2015, 16(12), 30133-30143; https://doi.org/10.3390/ijms161226205 - 17 Dec 2015

Cited by 22 | Viewed by 6859

Abstract

A heavy crude oil has been treated with deuterated alkylating reagents (CD₃I and C₂D₅I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron [...] Read more.

A heavy crude oil has been treated with deuterated alkylating reagents (CD₃I and C₂D₅I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) using electrospray ionization (ESI). The reaction of a polycyclic aromatic sulfur heterocycles (PASHs) dibenzothiophene (DBT), in the presence of silver tetrafluoroborate (AgBF₄) with ethyl iodide (C₂H₅I) in anhydrous dichloroethane (DCE) was optimized as a sample reaction to study heavy crude oil mixtures, and the reaction yield was monitored and determined by proton nuclear magnetic resonance spectroscopy (¹H-NMR). The obtained conditions were then applied to a mixture of standard aromatic CH-, N-, O- and S-containing compounds and then a heavy crude oil, and only sulfur-containing compounds were selectively alkylated. The deuterium labeled alkylating reagents, iodomethane-d₃ (CD₃I) and iodoethane-d₅ (C₂D₅I), were employed to the alkylation of heavy crude oil to selectively differentiate the tagged sulfur species from the original crude oil. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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720 KiB

Open AccessArticle

Determination of Oxidized Phosphatidylcholines by Hydrophilic Interaction Liquid Chromatography Coupled to Fourier Transform Mass Spectrometry

by Pia Sala, Sandra Pötz, Martina Brunner, Martin Trötzmüller, Alexander Fauland, Alexander Triebl, Jürgen Hartler, Ernst Lankmayr and Harald C. Köfeler

Int. J. Mol. Sci. 2015, 16(4), 8351-8363; https://doi.org/10.3390/ijms16048351 - 14 Apr 2015

Cited by 19 | Viewed by 6336

Abstract

A novel liquid chromatography-mass spectrometry (LC-MS) approach for analysis of oxidized phosphatidylcholines by an Orbitrap Fourier Transform mass spectrometer in positive electrospray ionization (ESI) coupled to hydrophilic interaction liquid chromatography (HILIC) was developed. This method depends on three selectivity criteria for separation and [...] Read more.

A novel liquid chromatography-mass spectrometry (LC-MS) approach for analysis of oxidized phosphatidylcholines by an Orbitrap Fourier Transform mass spectrometer in positive electrospray ionization (ESI) coupled to hydrophilic interaction liquid chromatography (HILIC) was developed. This method depends on three selectivity criteria for separation and identification: retention time, exact mass at a resolution of 100,000 and collision induced dissociation (CID) fragment spectra in a linear ion trap. The process of chromatography development showed the best separation properties with a silica-based Kinetex column. This type of chromatography was able to separate all major lipid classes expected in mammalian samples, yielding increased sensitivity of oxidized phosphatidylcholines over reversed phase chromatography. Identification of molecular species was achieved by exact mass on intact molecular ions and CID tandem mass spectra containing characteristic fragments. Due to a lack of commercially available standards, method development was performed with copper induced oxidation products of palmitoyl-arachidonoyl-phosphatidylcholine, which resulted in a plethora of lipid species oxidized at the arachidonoyl moiety. Validation of the method was done with copper oxidized human low-density lipoprotein (LDL) prepared by ultracentrifugation. In these LDL samples we could identify 46 oxidized molecular phosphatidylcholine species out of 99 possible candidates. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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1556 KiB

Open AccessArticle

Evaluation of a Method for Nitrotyrosine Site Identification and Relative Quantitation Using a Stable Isotope-Labeled Nitrated Spike-In Standard and High Resolution Fourier Transform MS and MS/MS Analysis

by Kent W. Seeley, Alison R. Fertig, Craig P. Dufresne, Joao P. C. Pinho and Stanley M. Stevens Jr.

Int. J. Mol. Sci. 2014, 15(4), 6265-6285; https://doi.org/10.3390/ijms15046265 - 14 Apr 2014

Cited by 11 | Viewed by 7227

Abstract

The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues [...] Read more.

The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues to form nitrotyrosine, and to date, the identification of nitrotyrosine sites in proteins continues to be a major analytical challenge. We have developed a method by which ¹⁵N-labeled nitrotyrosine groups are generated on peptide or protein standards using stable isotope-labeled peroxynitrite (O¹⁵NOO⁻), and the resulting standard is mixed with representative samples in which nitrotyrosine formation is to be measured by mass spectrometry (MS). Nitropeptide MS/MS spectra are filtered using high mass accuracy Fourier transform MS (FTMS) detection of the nitrotyrosine immonium ion. Given that the nitropeptide pair is co-isolated for MS/MS fragmentation, the nitrotyrosine immonium ions (at m/z = 181 or 182) can be used for relative quantitation with negligible isotopic interference at a mass resolution of greater than 50,000 (FWHM, full width at half-maximum). Furthermore, the standard potentially allows for the increased signal of nitrotyrosine-containing peptides, thus facilitating selection for MS/MS in a data-dependent mode of acquisition. We have evaluated the methodology in terms of nitrotyrosine site identification and relative quantitation using nitrated peptide and protein standards. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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3126 KiB

Open AccessArticle

Towards Lipidomics of Low-Abundant Species for Exploring Tumor Heterogeneity Guided by High-Resolution Mass Spectrometry Imaging

by Jonathan Cimino, David Calligaris, Johann Far, Delphine Debois, Silvia Blacher, Nor Eddine Sounni, Agnès Noel and Edwin De Pauw

Int. J. Mol. Sci. 2013, 14(12), 24560-24580; https://doi.org/10.3390/ijms141224560 - 17 Dec 2013

Cited by 24 | Viewed by 9380

Abstract

Many studies have evidenced the main role of lipids in physiological and also pathological processes such as cancer, diabetes or neurodegenerative diseases. The identification and the in situ localization of specific low-abundant lipid species involved in cancer biology are still challenging for both [...] Read more.

Many studies have evidenced the main role of lipids in physiological and also pathological processes such as cancer, diabetes or neurodegenerative diseases. The identification and the in situ localization of specific low-abundant lipid species involved in cancer biology are still challenging for both fundamental studies and lipid marker discovery. In this paper, we report the identification and the localization of specific isobaric minor phospholipids in human breast cancer xenografts by FTICR MALDI imaging supported by histochemistry. These potential candidates can be further confirmed by liquid chromatography coupled with electrospray mass spectrometry (LC-ESI-MS) after extraction from the region of interest defined by MALDI imaging. Finally, this study highlights the importance of characterizing the heterogeneous distribution of low-abundant lipid species, relevant in complex histological samples for biological purposes. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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Review

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945 KiB

Open AccessReview

Applications of Fourier Transform Ion Cyclotron Resonance (FT-ICR) and Orbitrap Based High Resolution Mass Spectrometry in Metabolomics and Lipidomics

by Manoj Ghaste, Robert Mistrik and Vladimir Shulaev

Int. J. Mol. Sci. 2016, 17(6), 816; https://doi.org/10.3390/ijms17060816 - 25 May 2016

Cited by 129 | Viewed by 13009

Abstract

Metabolomics, along with other “omics” approaches, is rapidly becoming one of the major approaches aimed at understanding the organization and dynamics of metabolic networks. Mass spectrometry is often a technique of choice for metabolomics studies due to its high sensitivity, reproducibility and wide [...] Read more.

Metabolomics, along with other “omics” approaches, is rapidly becoming one of the major approaches aimed at understanding the organization and dynamics of metabolic networks. Mass spectrometry is often a technique of choice for metabolomics studies due to its high sensitivity, reproducibility and wide dynamic range. High resolution mass spectrometry (HRMS) is a widely practiced technique in analytical and bioanalytical sciences. It offers exceptionally high resolution and the highest degree of structural confirmation. Many metabolomics studies have been conducted using HRMS over the past decade. In this review, we will explore the latest developments in Fourier transform mass spectrometry (FTMS) and Orbitrap based metabolomics technology, its advantages and drawbacks for using in metabolomics and lipidomics studies, and development of novel approaches for processing HRMS data. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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768 KiB

Open AccessReview

Fourier Transform Mass Spectrometry: The Transformation of Modern Environmental Analyses

by Lucy Lim, Fangzhi Yan, Stephen Bach, Katianna Pihakari and David Klein

Int. J. Mol. Sci. 2016, 17(1), 104; https://doi.org/10.3390/ijms17010104 - 14 Jan 2016

Cited by 11 | Viewed by 7291

Abstract

Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and [...] Read more.

Unknown compounds in environmental samples are difficult to identify using standard mass spectrometric methods. Fourier transform mass spectrometry (FTMS) has revolutionized how environmental analyses are performed. With its unsurpassed mass accuracy, high resolution and sensitivity, researchers now have a tool for difficult and complex environmental analyses. Two features of FTMS are responsible for changing the face of how complex analyses are accomplished. First is the ability to quickly and with high mass accuracy determine the presence of unknown chemical residues in samples. For years, the field has been limited by mass spectrometric methods that were based on knowing what compounds of interest were. Secondly, by utilizing the high resolution capabilities coupled with the low detection limits of FTMS, analysts also could dilute the sample sufficiently to minimize the ionization changes from varied matrices. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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1325 KiB

Open AccessReview

Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

by Navin Rauniyar

Int. J. Mol. Sci. 2015, 16(12), 28566-28581; https://doi.org/10.3390/ijms161226120 - 2 Dec 2015

Cited by 255 | Viewed by 20148

Abstract

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly [...] Read more.

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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1077 KiB

Open AccessReview

Developments in FTICR-MS and Its Potential for Body Fluid Signatures

by Simone Nicolardi, Bogdan Bogdanov, André M. Deelder, Magnus Palmblad and Yuri E. M. Van der Burgt

Int. J. Mol. Sci. 2015, 16(11), 27133-27144; https://doi.org/10.3390/ijms161126012 - 13 Nov 2015

Cited by 21 | Viewed by 6983

Abstract

Fourier transform mass spectrometry (FTMS) is the method of choice for measurements that require ultra-high resolution. The establishment of Fourier transform ion cyclotron resonance (FTICR) MS, the availability of biomolecular ionization techniques and the introduction of the Orbitrap™ mass spectrometer have widened the [...] Read more.

Fourier transform mass spectrometry (FTMS) is the method of choice for measurements that require ultra-high resolution. The establishment of Fourier transform ion cyclotron resonance (FTICR) MS, the availability of biomolecular ionization techniques and the introduction of the Orbitrap™ mass spectrometer have widened the number of FTMS-applications enormously. One recent example involves clinical proteomics using FTICR-MS to discover and validate protein biomarker signatures in body fluids such as serum or plasma. These biological samples are highly complex in terms of the type and number of components, their concentration range, and the structural identity of each species, and thus require extensive sample cleanup and chromatographic separation procedures. Clearly, such an elaborate and multi-step sample preparation process hampers high-throughput analysis of large clinical cohorts. A final MS read-out at ultra-high resolution enables the analysis of a more complex sample and can thus simplify upfront fractionations. To this end, FTICR-MS offers superior ultra-high resolving power with accurate and precise mass-to-charge ratio (m/z) measurement of a high number of peptides and small proteins (up to 20 kDa) at isotopic resolution over a wide mass range, and furthermore includes a wide variety of fragmentation strategies to characterize protein sequence and structure, including post-translational modifications (PTMs). In our laboratory, we have successfully applied FTICR “next-generation” peptide profiles with the purpose of cancer disease classifications. Here we will review a number of developments and innovations in FTICR-MS that have resulted in robust and routine procedures aiming for ultra-high resolution signatures of clinical samples, exemplified with state-of-the-art examples for serum and saliva. Full article

(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)

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