scholarly journals Resolving the microcosmos of complex samples: UPLC/travelling wave ion mobility separation high resolution mass spectrometry for the analysis of in vivo drug metabolism studies

2012 ◽  
Vol 16 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Stefan Blech ◽  
Ralf Laux
2015 ◽  
Vol 87 (8) ◽  
pp. 4321-4325 ◽  
Author(s):  
Paolo Benigni ◽  
Christopher J. Thompson ◽  
Mark E. Ridgeway ◽  
Melvin A. Park ◽  
Francisco Fernandez-Lima

2020 ◽  
Author(s):  
Elizabeth Neumann ◽  
Lukasz Migas ◽  
Jamie L. Allen ◽  
Richard Caprioli ◽  
Raf Van de Plas ◽  
...  

<div> <div> <p>Small metabolites are essential for normal and diseased biological function but are difficult to study because of their inherent structural complexity. MALDI imaging mass spectrometry (IMS) of small metabolites is particularly challenging as MALDI matrix clusters are often isobaric with metabolite ions, requiring high resolving power instrumentation or derivatization to circumvent this issue. An alternative to this is to perform ion mobility separation before ion detection, enabling the visualization of metabolites without the interference of matrix ions. Here, we use MALDI timsTOF IMS to image small metabolites at high spatial resolution within the human kidney. Through this, we have found metabolites, such as arginic acid, acetylcarnitine, and choline that localize to the cortex, medulla, and renal pelvis, respectively. We have also demonstrated that trapped ion mobility spectrometry (TIMS) can resolve matrix peaks from metabolite signal and separate both isobaric and isomeric metabolites with different localizations within the kidney. The added ion mobility data dimension dramatically increased the peak capacity for molecular imaging experiments. Future work will involve further exploring the small metabolite profiles of human kidneys as a function of age, gender, and ethnicity.</p></div></div>


Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1916
Author(s):  
Leticia Lacalle-Bergeron ◽  
Tania Portolés ◽  
Francisco J. López ◽  
Juan Vicente Sancho ◽  
Carolina Ortega-Azorín ◽  
...  

A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarkers associated with orange consumption (Citrus reticulata) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area.


Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 372 ◽  
Author(s):  
Priyanka Reddy ◽  
Aaron Elkins ◽  
Joanne Hemsworth ◽  
Kathryn Guthridge ◽  
Simone Vassiliadis ◽  
...  

Lolitrem B is the most potent indole-diterpene mycotoxin produced by Epichloë festucae var. lolii (termed LpTG-1), with severe intoxication cases reported in livestock. To date, there are no in vivo metabolism studies conducted for the mycotoxin. A mouse model assay established for assessing toxicity of indole-diterpenes was used to investigate metabolic products of lolitrem B. Mice were administered lolitrem B at 0.5 and 2.0 mg/kg body weight (b.wt) intraperitoneally before body and brain tissues were collected at 6 h and 24 h post-treatment. Samples were cryoground and subjected to a biphasic or monophasic extraction. The aqueous and lipophilic phases were analysed using liquid chromatography high-resolution mass spectrometry (LC–HRMS); data analysis was performed with Compound Discoverer™ software. A total of 10 novel phase I metabolic products were identified in the lipophilic phase and their distribution in the liver, kidney and various brain regions are described. The biotransformation products of lolitrem B were found to be present in low levels in the brain. Based on structure–activity postulations, six of these may contribute towards the protracted tremors exhibited by lolitrem B-exposed animals.


2020 ◽  
Vol 190 ◽  
pp. 113519
Author(s):  
Martin Uher ◽  
Martin Mžik ◽  
Jana Žďárová Karasová ◽  
David Herman ◽  
Lenka Čechová ◽  
...  

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