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- Forngren, B H, et al.
(författare)
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Determination of specific radioactivity for Br-76-labeled compounds measuring the ratio between Br-76 and Br-79 using packed capillary liquid chromatography mass spectrometry
- 2000
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 27:8, s. 851-853
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Tidskriftsartikel (refereegranskat)abstract
- Packed capillary liquid chromatography with electrospray mass spectrometry was used for direct determination of the specific radioactivity by calculation of isotope ratios between the Br-76- and Br-76-labeled analogues of N-((3 aminomethyl)benzyl) 4-bromobenzamide. Using 20 muL injections on packed capillary columns, sufficient mass sensitivity was attained for the determination on an injected amount of radioactivity corresponding to approximately 2 MBq (0.3 pmol of the Br-76 isotopic analogue). NUCL MED BIOL 27;6:851-853, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.
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- Kolmert, Johan, et al.
(författare)
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A quantitative LC/MS method targeting urinary 1-methyl-4-imidazoleacetic acid for safety monitoring of the global histamine turnover in clinical studies
- 2014
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 406:6, s. 1751-1762
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Tidskriftsartikel (refereegranskat)abstract
- Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-imidazoleacetic acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC-ESI-MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-imidazoleacetic acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3 %, respectively, at the mean urinary concentration level, while method accuracy was between -16.2 and 8.0 % across the linear concentration range of 22-1,111 ng mL(-1). Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 mu mol mmol(-1) of creatinine, and for male subjects, it was 2.1 mu mol mmol(-1) of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.
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- Nilsson, Anna, et al.
(författare)
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In Situ Mass Spectrometry Imaging and Ex Vivo Characterization of Renal Crystalline Deposits Induced in Multiple Preclinical Drug Toxicology Studies
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e47353-
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Tidskriftsartikel (refereegranskat)abstract
- Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ. Two potential microsomal prostaglandin E synthase 1 inhibitors, with similar chemical structure, were administered to rats over a seven day period. This resulted in kidney damage with marked tubular degeneration/regeneration and crystal deposits within the tissue that was detected by histopathology. Results from direct tissue section analysis by matrix-assisted laser desorption ionization mass spectrometry imaging were combined with data obtained following manual crystal dissection analyzed by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical composition of the crystal deposits was successfully identified as a common metabolite, bisulphonamide, of the two drug candidates. In addition, an un-targeted analysis revealed molecular changes in the kidney that were specifically associated with the area of the tissue defined as pathologically damaged. In the presented study, we show the usefulness of combining mass spectrometry imaging with an array of powerful analytical tools to solve complex toxicological problems occurring during drug development.
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