Identification of a Crystalline Drug Metabolite in Tissue Sections using Microscopy and Maldi-MS

2000 ◽  
Vol 6 (S2) ◽  
pp. 1002-1003
Author(s):  
J. Fagerland ◽  
L. Miesbauer ◽  
R. Burton ◽  
F. Seiler ◽  
J. Neilly ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Metabolic Pathways ◽  
Renal Toxicity ◽  
Polarized Light ◽  
Parent Drug ◽  
Maldi Ms ◽  
Drug Candidate ◽  
Ionization Mass ◽  
X Ray ◽  
Tissue Sections

Development of a potential drug candidate was discontinued when rats treated with the compound developed severe renal toxicity after one week of daily dosing. Tubular degeneration in the kidney was accompanied by deposition of large amounts of crystalline material, which was also present in spleen and pancreas (Fig. 1). It was presumed that the crystals were precipitated parent drug or one of its metabolites. Using microscopy and mass spectrometry, it was confirmed that the crystals were indeed derived from the drug and not endogenously formed; in addition, the precise metabolite that had precipitated in the tissues was identified, providing clues to the metabolic pathways involved.Frozen sections of phosphate-buffered formaldehyde-fixed kidney, pancreas, and spleen were evaluated by polarized light microscopy (PLM), scanning electron microscopy (SEM) with energy dispersive x-ray spectroscopy (EDXS), and matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS). For reference, crystals of the trifluoroacetate salt of the parent drug were also analyzed using these methods.

scholarly journals MALDIViz: A Comprehensive Informatics Tool for MALDI-MS Data Visualization and Analysis

2017 ◽  
Vol 22 (10) ◽  
pp. 1246-1252 ◽  
Author(s):  
Kishore Kumar Jagadeesan ◽  
Simon Ekström
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
High Throughput Screening ◽  
Web Application ◽  
Low Cost ◽  
Maldi Ms ◽  
Ionization Mass ◽  
Label Free ◽  
Label Free Detection ◽  
R Shiny

Recently, mass spectrometry (MS) has emerged as an important tool for high-throughput screening (HTS) providing a direct and label-free detection method, complementing traditional fluorescent and colorimetric methodologies. Among the various MS techniques used for HTS, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides many of the characteristics required for high-throughput analyses, such as low cost, speed, and automation. However, visualization and analysis of the large datasets generated by HTS MALDI-MS can pose significant challenges, especially for multiparametric experiments. The datasets can be generated fast, and the complexity of the experimental data (e.g., screening many different sorbent phases, the sorbent mass, and the load, wash, and elution conditions) makes manual data analysis difficult. To address these challenges, a comprehensive informatics tool called MALDIViz was developed. This tool is an R-Shiny-based web application, accessible independently of the operating system and without the need to install any program locally. It has been designed to facilitate easy analysis and visualization of MALDI-MS datasets, comparison of multiplex experiments, and export of the analysis results to high-quality images.

Multiphoton and soft X-ray ionization mass spectrometry

1992 ◽  
pp. 191-220
Author(s):  
U. Boesl ◽  
J. Grotemeyer ◽  
K. Müller-Dethlefs ◽  
H.J. Neusser ◽  
H.L. Selzle ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
X Ray

scholarly journals Reaction with Proteins of a Five-Coordinate Platinum(II) Compound

2019 ◽  
Vol 20 (3) ◽  
pp. 520 ◽  
Author(s):  
Giarita Ferraro ◽  
Tiziano Marzo ◽  
Maria Cucciolito ◽  
Francesco Ruffo ◽  
Luigi Messori ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Platinum Complexes ◽  
Rnase A ◽  
Side Chain ◽  
Planar Geometry ◽  
Ionization Mass ◽  
X Ray ◽  
X Ray Crystallography ◽  
Egg White Lysozyme ◽  
Square Planar

Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein–metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species.

scholarly journals Rapid Alterations in Cerebral White Matter Lipid Profiles After Ischemic-Reperfusion Brain Injury in Fetal Sheep as Demonstrated by MALDI-Mass Spectrometry

2019 ◽  
Vol 22 (4) ◽  
pp. 344-355 ◽  
Author(s):  
Gina M Gallucci ◽  
Ming Tong ◽  
Xiaodi Chen ◽  
Barbara S Stonestreet ◽  
Amy Lin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
White Matter ◽  
Lipid Composition ◽  
Lipid Profiles ◽  
Maldi Ms ◽  
Cerebral White Matter ◽  
Ionization Mass ◽  
Myelin Lipid ◽  
Fetal Sheep ◽  
Bilateral Carotid

Background Perinatal ischemia-reperfusion (I/R) injury of cerebral white matter causes long-term cognitive and motor disabilities in children. I/R damages or kills highly metabolic immature oligodendroglia via oxidative stress, excitotoxicity, inflammation, and mitochondrial dysfunction, impairing their capacity to generate and maintain mature myelin. However, the consequences of I/R on myelin lipid composition have not been characterized. Objective This study utilized matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to assess alterations in cerebral supraventricular white matter myelin lipid profiles in a fetal sheep model of perinatal I/R. Methods Fetal sheep (127 days gestation) were studied after 30 minutes of bilateral carotid artery occlusion followed by 4 (n = 5), 24 (n = 7), 48 (n = 3), or 72 (n = 5) hours of reperfusion, or sham treatment (n = 5). White matter lipids were analyzed by negative ion mode MALDI-MS. Results Striking I/R-associated shifts in phospholipid and sphingolipid expression occurred over the 72-hour time course with most responses detected within 4 hours of reperfusion and progressing at the 48- and 72-hour points. I/R decreased expression of phosphatidic acid and phosphatidylethanol amine and increased phosphatidylinositol, sulfatide, and lactosylceramide. Conclusions Cerebral I/R in mid-gestation fetal sheep causes rapid shifts in white matter myelin lipid composition that may reflect injury, proliferation, or recovery of immature oligodendroglia.

Analysis for Parent Drug and Drug Metabolite in Rat Liver, Bile Stones, and Bile Using Microscopy, Laser Capture Microdissection and Analytical Chemistry Techniques

2001 ◽  
Vol 7 (S2) ◽  
pp. 632-633
Author(s):  
J. Neilly ◽  
G. Gagne ◽  
A. Vogt ◽  
J. Fagerland ◽  
L. Miesbauer ◽  
...  
Keyword(s):  
Analytical Chemistry ◽  
Parent Drug ◽  
Drug Candidate ◽  
Tissue Sections ◽  
Toxicology Study ◽  
Uv Illumination ◽  
Drug Metabolite ◽  
Bulk Drug ◽  
Effective Use

Microscopy, microdissection, and analytical chemistry techniques were used to localize and identify drug and drug metabolites in specimens from drug-treated rats. During a toxicology study in rats of a drug candidate, concretions (stones) were found in the common bile duct, and pigmented material was found in hepatocytes and liver macrophages after long-term exposure to the drug. Because a recent study showed the effective use of microscopy and mass spectrometry (MS) to identify drug metabolite in tissue sections, we used similar methods to confirm that pigmented material in liver cells was drug metabolite. Energy dispersive x-ray spectroscopy (EDS) suggested that drug and/or metabolite were also present in stones.Pigmented hepatocytes and macrophages in frozen sections of unfixed liver exhibited fluorescence similar to that of parent drug. When excited by UV illumination, these cells fluoresced the same color blue as the bulk drug (Fig. 1).

scholarly journals [Ni(OH)3W6O18(OCH2)3CCH2OH]4−: the first tris-functionalized Anderson-type heteropolytungstate

2016 ◽  
Vol 52 (59) ◽  
pp. 9263-9266 ◽  
Author(s):  
Nadiia I. Gumerova ◽  
Alexander Roller ◽  
Annette Rompel
Keyword(s):  
Mass Spectrometry ◽  
Ir Spectroscopy ◽  
Single Crystal ◽  
Electrospray Ionization ◽  
Electrospray Ionization Mass Spectrometry ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
X Ray Diffraction ◽  
X Ray

Na2[TMA]2[Ni(OH)3W6O18(OCH2)3CCH2OH]·9H2O represents the first covalent tris-functionalized Anderson-type heteropolytungstate and was characterized by single-crystal X-ray diffraction, electrospray ionization mass spectrometry, TGA and IR spectroscopy.

Nitrogen speciation in fine and coarse clay fractions of a Cryoboroll - new evidence from pyrolysis-mass spectrometry and nitrogen K-edge XANES

2010 ◽  
Vol 90 (2) ◽  
pp. 309-318 ◽  
Author(s):  
P. Leinweber ◽  
G. Jandl ◽  
K -U. Eckhardt ◽  
J. Kruse ◽  
F L Walley ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Major Constituent ◽  
Organic N ◽  
Ionization Mass ◽  
Pyrolysis Mass Spectrometry ◽  
Edge Structure ◽  
X Ray ◽  
Soil Clay ◽  
New Evidence ◽  
X Ray Absorption

Soil clay fractions are usually enriched in nitrogen (N), but the chemical identity of this N is largely unknown. Therefore, we investigated organic N in fine and coarse clay of a clay-rich Cryoboroll by Curie-point pyrolysis-gas chromatography/mass spectrometry (Cp Py-GC/MS), Pyrolysis-field ionization mass spectroscopy (Py-FIMS) and synchrotron-based nitrogen K-edge X-ray absorption near edge structure (N-XANES) spectroscopy. The Cp Py-GC-MS revealed 30 structurally different N-containing compounds, such as substituted pyridines, pyrroles; pyrazines, pyrazoles, imidazoles, quinolines, side-chain N-containing benzenes, and single compounds of substituted benzotriazole, purine and indole. These accounted for about 10% of peak area in the Py-GC chromatograms. The Py-FIMS and N-XANES spectra indicated interlayer-NH4+ and revealed pyridinic and nitrilic N compounds, but disagreed in the proportions of pyrroles. All three complementary methods confirmed to different extents previous wet-chemical data on N-fractions in these samples, and provided new evidence for about 30 to 40% non-proteinaceous N as major constituent of the so-called “unknown organic N” in soil. Key words: Soil clay, organic matter, pyrolysis-mass spectrometry, synchrotron, X-ray absorption, NEXAFS

scholarly journals Application of dyes as doping agents in MALDI-MS matrices for the signal enhancement of proteins

RSC Advances ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. 6598-6604
Author(s):  
Arslan Ali ◽  
Najia Shahid ◽  
Syed Ghulam Musharraf
Keyword(s):  
Mass Spectrometry ◽  
Laser Desorption ◽  
Maldi Ms ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
Laser Desorption Ionization ◽  
As Doping ◽  
Desorption Ionization ◽  
Matrix Assisted Laser ◽  
Matrix Assisted Laser Desorption

Dyes can significantly influence the ionization of proteins, when used as dopants in conventional matrices used for Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS).

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