| 1. |
- Maddalo, Gianluca, et al.
(author)
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Porcine P2 myelin protein primary structure and bound fatty acids determined by mass spectrometry
- 2010
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In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 397:5, s. 1903-1910
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Journal article (peer-reviewed)abstract
- Complementary collision-induced/electron capture dissociation Fourier-transform ion cyclotron resonance mass spectrometry was used to fully sequence the protein P2 myelin basic protein. It is an antigenic fatty-acid-binding protein that can induce experimental autoimmune neuritis: an animal model of Guillain-Barre syndrome, a disorder similar in etiology to multiple sclerosis. Neither the primary structure of the porcine variant, nor the fatty acids bound by the protein have been well established to date. A 1.8-angstrom crystal structure shows but a bound ligand could not be unequivocally identified. A protocol for ligand extraction from protein crystals has been developed with subsequent gas chromatography MS analysis allowing determination that oleic, stearic, and palmitic fatty acids are associated with the protein. The results provide unique and general evidence of the utility of mass spectrometry for characterizing proteins from natural sources and generating biochemical information that may facilitate attempts to elucidate the causes for disorders such as demyelination.
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| 2. |
- Shariatgorji, Mohammadreza, et al.
(author)
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Controlled-pH Tissue Cleanup Protocol for Signal Enhancement of Small Molecule Drugs Analyzed by MALDI-MS Imaging
- 2012
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 84:10, s. 4603-4607
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Journal article (peer-reviewed)abstract
- The limit of detection of low-molecular weight compounds in tissue sections, analyzed by matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), was significantly improved by employing sample washing using a pH-controlled buffer solution. The pH of the washing solutions were set at values whereby the target analytes would have low solubility. Washing the tissue sections in the buffered solution resulted in removal of endogenous soluble ionization-suppressing compounds and salts, while the target compound remained in situ with minor or no delocalization during the buffered washing procedure. Two pharmaceutical compounds (cimetidine and imipramine) and one new protease inhibitor compound were successfully used to evaluate the feasibility of the pH-controlled tissue washing protocol for MALDI-MSI. Enhancement in signal-to-noise ratio was achieved by a factor of up to 10.
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| 3. |
- Källback, Patrik, et al.
(author)
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Cross-validated Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Quantitation Protocol for a Pharmaceutical Drug and Its Drug-Target Effects in the Brain Using Time-of-Flight and Fourier Transform Ion Cyclotron Resonance Analyzers
- 2020
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 92:21, s. 14676-14684
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Journal article (peer-reviewed)abstract
- Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an established tool in drug development, which enables visualization of drugs and drug metabolites at spatial localizations in tissue sections from different organs. However, robust and accurate quantitation by MALDI-MSI still remains a challenge. We present a quantitative MALDI-MSI method using two instruments with different types of mass analyzers, i.e., time-of-flight (TOF) and Fourier transform ion cyclotron resonance (FTICR) MS, for mapping levels of the in vivo-administered drug citalopram, a selective serotonin reuptake inhibitor, in mouse brain tissue sections. Six different methods for applying calibration standards and an internal standard were evaluated. The optimized method was validated according to authorities' guidelines and requirements, including selectivity, accuracy, precision, recovery, calibration curve, sensitivity, reproducibility, and stability parameters. We showed that applying a dilution series of calibration standards followed by a homogeneously applied, stable, isotopically labeled standard for normalization and a matrix on top of the tissue section yielded similar results to those from the reference method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The validation results were within specified limits and the brain concentrations for TOF MS (51.1 +/- 4.4 pmol/mg) and FTICR MS (56.9 +/- 6.0 pmol/mg) did not significantly differ from those of the cross-validated LC-MS/MS method (55.0 +/- 4.9 pmol/mg). The effect of in vivo citalopram administration on the serotonin neurotransmitter system was studied in the hippocampus, a brain region that is the principal target of the serotonergic afferents along with the limbic system, and it was shown that serotonin was significantly increased (2-fold), but its metabolite 5-hydroxyindoleacetic acid was not. This study makes a substantial step toward establishing MALDI-MSI as a fully quantitative validated method.
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| 4. |
- Shariatgorji, Mohammadreza, et al.
(author)
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Bromopyrylium Derivatization Facilitates Identification by Mass Spectrometry Imaging of Monoamine Neurotransmitters and Small Molecule Neuroactive Compounds
- 2020
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In: Journal of the American Society for Mass Spectrometry. - : AMER CHEMICAL SOC. - 1044-0305 .- 1879-1123. ; 31:12, s. 2553-2557
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Journal article (peer-reviewed)abstract
- Mass spectrometry imaging using matrix-assisted laser desorption/ionization and desorption electrospray ionization has recently been employed to investigate the distribution of neurotransmitters, including biogenic amines and amino acids, directly in brain tissue sections. Ionization is facilitated by charge-tagging through pyrylium derivatization of primary amine containing neurotransmitters directly in tissue sections, significantly improving the limit of detection. Since the derivatization adds carbon and hydrogen to the target compounds, the resulting isotopic patterns of the products are not distinctive from those of the nonderivatized species. Here, we describe an approach for chemically modifying the reactive pyrylium ion to introduce the distinct isotopic signature of bromine in mass spectra of chemically derivatized substances in tissue sections. The method enables monoamine compounds to be distinguished directly in tissue sections, facilitating their identification.
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| 5. |
- Shariatgorji, Mohammadreza, et al.
(author)
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Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging
- 2019
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In: Nature Methods. - : NATURE PUBLISHING GROUP. - 1548-7091 .- 1548-7105. ; 16:10, s. 1021-1028
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Journal article (peer-reviewed)abstract
- We present a mass spectrometry imaging (MSI) approach for the comprehensive mapping of neurotransmitter networks in specific brain regions. Our fluoromethylpyridinium-based reactive matrices facilitate the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups, including dopaminergic and serotonergic neurotransmitters and their associated metabolites. These matrices improved the matrix-assisted laser desorption/ionization (MALDI)-MSI detection limit toward low-abundance neurotransmitters and facilitated the simultaneous imaging of neurotransmitters in fine structures of the brain at a lateral resolution of 10 mu m. We demonstrate strategies for the identification of unknown molecular species using the innate chemoselectivity of the reactive matrices and the unique isotopic pattern of a brominated reactive matrix. We illustrate the capabilities of the developed method on Parkinsonian brain samples from human post-mortem tissue and animal models. The direct imaging of neurotransmitter systems provides a method for exploring how various neurological diseases affect specific brain regions through neurotransmitter modulation.
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| 6. |
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| 7. |
- Shariatgorji, Mohammadreza, et al.
(author)
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Trends in the bioanalytical applications of microfluidic electrocapture
- 2011
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In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 399:1, s. 191-195
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Journal article (other academic/artistic)abstract
- Downscaled analytical tools for sample preparation have offered benefits such as higher throughput, easier automation and lower sample/reagent consumption. Microfluidic electrocapture, which is a newly developed sample preparation/manipulation system, uses an electric field to trap and separate charged species without using any solid sorbent. The feasibility of using microfluidic electrocapture is reported for separation, clean-up, concentration, microreactions and complexation studies of proteins, peptides and other biologically important biomolecules. The instrumentation and applications of microfluidic electrocapture are reviewed and an overview is provided of future perspectives offered by the current and envisaged platforms.
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| 8. |
- Shariatgorji, Mohammadreza, et al.
(author)
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Deuterated Matrix-Assisted Laser Desorption Ionization Matrix Uncovers Masked Mass Spectrometry Imaging Signals of Small Molecules
- 2012
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 84:16, s. 7152-7157
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Journal article (peer-reviewed)abstract
- D-4-alpha-Cyano-4-hydroxycinnamic acid (D-4-CHCA) has been synthesized for use as a matrix for matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) and MALDI-MS imaging (MSI) of small molecule drugs and endogenous compounds. MALDI-MS analysis of small molecules has historically been hindered by interference from matrix ion clusters and fragment peaks that mask signals of low molecular weight compounds of interest. By using D-4-CHCA, the cluster and fragment peaks of CHCA, the most common matrix for analysis of small molecules, are shifted by + 4, + 8 and + 12 Da, which expose signals across areas of the previously concealed low mass range. Here, obscured MALDI-MS signals of a synthetic small molecule pharmaceutical, a naturally occurring isoquinoline alkaloid, and endogenous compounds including the neurotransmitter acetylcholine have been unmasked and imaged directly from biological tissue sections.
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