Uwe Karst

University of Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (265)973.37 Total impact

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    ABSTRACT: This work presents a quantitative bioimaging method for platinum based on laser ablation-inductively coupled plasma-mass spectrometry and its application for a biomedical study concerning toxic side effects of cisplatin. To trace the histopathology back to cisplatin, platinum was localized and quantified in major functional units of testicle, cochlea, kidney, nerve and brain sections from cisplatin treated mice. The direct consideration of the histology enables precise interpretation of the Pt images and the novel quantitative evaluation approach allows significantly more precise investigations than the pure image. For the first time, platinum was detected and quantified in all major injured structures including organ of Corti of cochlea and seminiferous tubule of testicle. In this way, proximal tubule in kidney, Leydig cells in testicle, stria vascularis and organ of Corti in cochlea and nerve fibers in sciatic nerves are confirmed as targets of cisplatin in these organs. However, the accumulation of platinum in almost all investigated structures also raises questions about more complex pathogenesis including direct and indirect interruption of several biological processes.
    Metallomics 10/2015; DOI:10.1039/c5mt00226e · 3.59 Impact Factor
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    ABSTRACT: The interaction of mercury species with human erythrocytes is studied to investigate possible high molecular binding partners for mercury species. Human blood hemolysate was spiked with methylmercury and investigated by means of liquid chromatography (LC) coupled to electrospray ionization time of flight mass spectrometry (ESI-ToF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Beside adduct formation of mercury species with hemoglobin, the main compound of the erythrocytes, mercury binding to the enzyme carbonic anhydrase was revealed. Due to an enzymatic digest of the protein-mercury adduct, the binding site at the free thiol group of the protein was identified. These results indicate that carbonic anhydrase might play a role in mercury toxicity.
    Metallomics 10/2015; DOI:10.1039/C5MT00186B · 3.59 Impact Factor
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    ABSTRACT: The uptake of mercury species in the model organism Drosophila melanogaster was investigated by elemental bioimaging using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The mercury distribution in Drosophila melanogaster was analyzed for the three species mercury(II) chloride, methylmercury chloride and thimerosal after intoxication. A respective analytical method was developed and applied to the analysis of entire Drosophila melanogaster first, before a particular focus was directed to the cerebral areas of larvae and adult flies. For quantification of mercury, matrix-matched standards based on gelatin were prepared. Challenges of spatially dissolved mercury determination, namely strong evaporation issues of the analytes and an inhomogeneous distribution of mercury in the standards due to interactions with cysteine containing proteins of the gelatin were successfully addressed by complexation with meso-2,3-dimercaptosuccinic acid (DMSA). No mercury was detected in the cerebral region for mercury(II) chloride, whereas both organic species showed the ability to cross the blood-brain barrier. Quantitatively, the mercury level in the brain exceeded the fed concentration indicating mercury enrichment, which was approximately three times higher for methylmercury chloride than for thimerosal.
    Analytical Chemistry 10/2015; DOI:10.1021/acs.analchem.5b02500 · 5.64 Impact Factor
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    ABSTRACT: A laser ablation system (LA) was coupled to an in-house developed low-flow inductively coupled plasma ion source for mass spectrometry (ICP-MS). In this setup, the low-flow torch showed best analytical performance at a total argon gas flow rate of only 1.27 L min-1 and a generator power of 900 W. The optimized system was applied to elemental bioimaging. Two different sections of one kidney sample were analyzed and images of the elements Al and Br from the staining agents hematoxylin and eosin, respectively, and I from a contrast agent iodixanol were recorded selectively and with high sensitivity. For detection of the elements, the mass traces 27Al, 79Br, 81Br, and 127I were selected to demonstrate the system's analytical performance over a wide mass range. In total, the argon consumption could be reduced by >90% compared to conventional ICP-MS systems.
    Journal of Analytical Atomic Spectrometry 10/2015; 30(10). DOI:10.1039/C5JA00199D · 3.47 Impact Factor
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    ABSTRACT: Elemental bio-imaging (EBI) of trace metal distributions in tissue sections is typically performed by laser ablation-single quadrupole-inductively coupled plasma-mass spectrometry (LA-ICP-SQ-MS) in which the sensitivity of biologically relevant elements such as Fe may be inhibited by polyatomic interferences. The triple quadrupole ICP-MS (ICP-QQQ-MS) is designed to reduce interferences and was examined for its potential application to EBI. Three tune modes; a no-gas, an H2, and an O2/H2 tune were developed and investigated for their suitability. All three performed well with high signal to noise ratios and low limits of detection. The O2/H2 tune was applied to a prostate cancer biopsy sample, with high levels of Zn found in the area correlating with the cancer. The oxygen mass shift was applied to image P and Se in a mouse brain. The unique focussing properties of the ICP-QQQ-MS and the ability to use mixed cell gases provided sensitive analyses of all measured isotopes with the O2/H2 tune, including those unaffected by mass shift reactions.
    Journal of Analytical Atomic Spectrometry 09/2015; DOI:10.1039/C5JA00293A · 3.47 Impact Factor
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    ABSTRACT: A specific labeling method for cysteine moieties in proteins was developed. Electrochemical oxidation of phenolic compounds such as phenol or acetaminophen leads to the generation of the reactive intermediates benzoquinone and N-acetyl-p-benzoquinone imine, which can subsequently react with nucleophilic thiol functions in peptides or proteins. Differential labeling of cysteine residues was successfully demonstrated with native as well as heavy-isotope labeled forms of the corresponding labeling compounds. The specific mass differences on the peptide level were successfully analyzed by mass spectrometry for the tripeptide glutathione. Free cysteines in various proteins such as β-lactoglobulin A, human serum albumin, hemoglobin and human carbonic anhydrase I were successfully labeled. Tryptic digestion of differentially labeled carbonic anhydrase I and hemoglobin allowed the identification of the binding site in the proteins. The obtained mass difference allowed an easy identification of the cysteine containing peptides. With these experiments, it was successfully demonstrated that the developed method can serve as a tool for counting cysteine moieties in proteins and, thus, be used as additional technique in protein identification experiments.
    Analytical Chemistry 09/2015; 87(19). DOI:10.1021/acs.analchem.5b02497 · 5.64 Impact Factor
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    ABSTRACT: Thyroxine (T4) is one of the major thyroid hormones, which regulates cellular metabolism, central nervous system development, body temperature, reproduction and growth. The simulation of oxidation reactions of T4 may provide further information about the fate of T4 in cells without using laborious in vitro and susceptible in vivo tests. In this study, oxidation products of T4, generated inside an electrochemical (EC) cell, were separated and identified by on-line EC/liquid chromatography/electrospray ionization-mass spectrometry (EC/LC/ESI-MS). In another experimental setup, the electrogenerated metabolites were separated by LC, subsequently mixed with a compensating countergradient (cg), and finally introduced into an inductively coupled plasma-mass spectrometer (ICP-MS). The gradient compensation was achieved by an additional pump module which generated a reversed gradient to the analytical gradient used for the separation. This setup enabled a constant composition of the LC eluent flowing into the plasma so that stable plasma conditions and a uniform response over the complete elution time could be achieved. Combined with identification information from online-coupled EC/LC/ESI-MS, robust and reliable quantification of T4 and its oxidation products was accomplished by on-line coupled EC/cgLC/ICP-MS, with LOD of 33nM of iodine.
    Journal of Chromatography A 09/2015; DOI:10.1016/j.chroma.2015.09.076 · 4.17 Impact Factor
  • Rebecca Niehaus · Michael Sperling · Uwe Karst ·
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    ABSTRACT: A 213nm Nd:YAG laser ablation system (LA) coupled to a quadrupole ICP-MS was used to ablate thin slices of gelatin and Technovit, both commonly used as standard materials for bioimaging applications. Particle sizes and their distribution within the ablated aerosols were investigated using an optical particle counter. A considerably larger number of particles above 0.3µm was found for Technovit, while the gelatin aerosol carried mostly particles in the lower nm regime. Increasing the laser fluence during ablation resulted in a larger number of µm sized particles for both materials. Subsequently, fractionation effects during the material transport into the ICP and the ionization within the ICP were analyzed. An increase in the transportation tube length resulted in a signal broadening for shot experiments, but no material loss was observed. A comparison of ionization characteristics of gelatin particles ablated within the LA to wet aerosol particles introduced via nebulization showed similar ionization efficiencies for both aerosols, but the vaporization of gelatin particles required a prolonged time. Additionally, fractionation during the ablation process in gelatin was studied by recording isotope ratios of spiked standards for varying laser fluence. Results indicate a strong deviation from the expected ratio for laser fluences close to the threshold for ablation.
    Journal of Analytical Atomic Spectrometry 07/2015; 30(10). DOI:10.1039/C5JA00221D · 3.47 Impact Factor
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    20th International C. elegans Meeting, Los Angeles, USA; 06/2015
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    ABSTRACT: RationalePotentially performance-enhancing agents, particularly anabolic agents, are advertised and distributed by Internet-based suppliers to a substantial extent. Among these anabolic agents, a substance referred to as LGD-4033 has been made available, comprising the core structure of a class of selective androgen receptor modulators (SARMs).Methods In order to provide comprehensive analytical data for doping controls, the substance was obtained and characterized by nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography/electrospray ionization high resolution/high accuracy tandem mass spectrometry (LC/ESI-HRMS). Following the identification of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile, the substance was subjected to in vitro metabolism studies employing human liver microsomes and Cunninghamella elegans (C. elegans) preparations as well as electrochemical metabolism simulations.ResultsBy means of LC/ESI-HRMS, five main phase-I metabolites were identified as products of liver microsomal preparations including three monohydroxylated and two bishydroxylated species. The two most abundant metabolites (one mono- and one bishydroxylated product) were structurally confirmed by LC/ESI-HRMS and NMR. Comparing the metabolic conversion of 4-(2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile observed in human liver microsomes with C. elegans and electrochemically derived metabolites, one monohydroxylated product was found to be predominantly formed in all three methodologies.Conclusions The implementation of the intact SARM-like compound and its presumed urinary phase-I metabolites into routine doping controls is suggested to expand and complement existing sports drug testing methods. Copyright © 2015 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 06/2015; 29(11). DOI:10.1002/rcm.7189 · 2.25 Impact Factor
  • Lars Büter · Martin Vogel · Uwe Karst ·
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    ABSTRACT: Electrochemistry (EC) has turned out to be a valuable tool for the elucidation of reactive oxidation products of pharmaceuticals and ingredients of personal-care products when investigating the affinity towards biomolecules, such as peptides or proteins containing nucleophilic groups. The combination of EC with liquid chromatography (LC) and mass spectrometry (MS) allows investigation of adduct formation, identification of reactive metabolites prior to binding, localization of active binding sites in a biomolecule and monitoring of isomer formation. The first part provides an overview on studies on formation of covalent conjugates. The second part presents several methods, which are dedicated to tagging cysteine moieties in biomolecules. The generation of electrophilic intermediates enables the selective reaction of these species with the nucleophilic thiol group in cysteine. Thus, counting of cysteines in proteins and mass fingerprinting of cysteine containing tryptic peptides is accomplished.
    TrAC Trends in Analytical Chemistry 05/2015; 70. DOI:10.1016/j.trac.2015.03.009 · 6.47 Impact Factor
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    ABSTRACT: Cis-diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 µm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.
    Metallomics 05/2015; 7(7). DOI:10.1039/C5MT00096C · 3.59 Impact Factor
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    ABSTRACT: One of the most common setups for elemental bioimaging, the hyphenation of a laser ablation (LA) system and an inductively coupled plasma mass spectrometer (ICP-MS), was expanded by adding full scan mass spectrometric information as another dimension of information. While most studies deal with the analysis of typically not more than up to 10 isotopes per scan cycle, a fast scanning quadrupole mass analyzer was utilized to record the full mass spectrum of interest in this work. Mass-to-charge ratios from 6 to 250 were observed within one cycle. Besides the x- and y-position on the ablated sample and the intensity, the m/z-ratio served as fourth variable for each pixel of the obtained data, closing thereby the gap between “inorganic” and “organic” mass spectrometric imaging techniques. The benefits of this approach include an improved control of interferences, the discovery of unexpected elemental distributions, the possibility to plot isotopic ratios, and to integrate the intensities of a certain number of mass channels recorded for each isotope, thus virtually increasing sensitivity. The respective data are presented for dried droplets as well as embedded animal and human tissue slices. Limits of detection were calculated and found to be in accordance with counting statistics. A dedicated software macro was developed for data manipulation prior to common evaluation and image creation. Graphical Abstract ᅟ
    Journal of the American Society for Mass Spectrometry 05/2015; 26(8). DOI:10.1007/s13361-015-1141-y · 2.95 Impact Factor
  • Rainer Bischoff · Uwe Karst ·

    TrAC Trends in Analytical Chemistry 05/2015; DOI:10.1016/j.trac.2015.04.008 · 6.47 Impact Factor
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    ABSTRACT: Due to the fact that cellular therapies are increasingly finding application in clinical trials and promise success by treatment of fatal diseases, monitoring strategies to investigate the delivery of the therapeutic cells to the target organs are getting more and more into the focus of modern in vivo imaging methods. In order to monitor the distribution of the respective cells, they can be labeled with lanthanide complexes such as thulium-1,4,7,10-tetraazacyclodoecane-α,α,α,α-tetramethyl-1,4,7,10-tetraacetic acid (Tm(DOTMA)). In this study, experiments on a mouse model with two different cell types, namely tumor cells and macrophages labeled with Tm-DOTMA, were performed. The systemic distribution of Tm(DOTMA) of both cell types was investigated by means of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Using the high resolution of 25 µm, distribution maps of Tm in different tissues such as tumor, liver, lung, spleen as well as in explanted gel pellets were generated and the behavior of the labeled cells inside the tissue was investigated. Additionally, quantitative data were obtained using homemade matrix-matched standards based on egg yolk. Using this approach, limits of detection and quantification of 2.2 ng·g-1 and 7.4 ng·g-1, respectively, and an excellent linearity over the concentration range from 0.01 to 46 µg·g-1 was achieved. The highest concentration of the label agent, 32.6 µg·g-1, in tumor tissue was ob-served in the area of the injection of the labeled tumor cells. Regarding the second experiment with macrophages for cell tracking, Tm was detected in the explanted biogell pellet with relatively low concentrations below 60 ng·g-1 and in the liver with relatively high concentration of 10 ng·g-1. Besides thulium, aluminum was detected with equal distribution behavior in the tumor section due to a contamination resulting from the labeling procedure, which includes the usage of an Al electrode.
    Analytical Chemistry 03/2015; 87(8). DOI:10.1021/ac504363q · 5.64 Impact Factor
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    ABSTRACT: The cover picture shows dendrimer-encapsulated Pd nanoparticles (NPs), anchored within a continuous-flow microreactor, that efficiently catalyze the Suzuki–Miyaura cross-coupling (SMC) of iodobenzene and p-tolylboronic acid. The different dendrimer generations employed in this study are represented by the size and the ramification of the trees. Pd NPs are entrapped within the trees along the shore, which is “washed” by the river, symbolizing the laminar flow within the microreactor. In their Full Paper, R. Ricciardi et al. show the influence of the dendrimer generation on the catalytic activity of the Pd NPs. The article highlighted by this cover can be found on p. 936 ff. of Issue 6, 2015.
    ChemCatChem 03/2015; 7(6):875-875. DOI:10.1002/cctc.201590030 · 4.56 Impact Factor
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    ABSTRACT: The combined use of elemental bioimaging and speciation analysis is presented as a novel means for the diagnosis of nephrogenic systemic fibrosis (NSF), a rare disease occurring after administration of gadolinium-based contrast agents (GBCA) for magnetic resonance imaging (MRI), in skin samples of patients suffering from renal insufficiency. As the pathogenesis of NSF is still largely unknown particularly with regard to the distribution and potential retention of gadolinium in the human organism, a skin biopsy ample from a suspected NSF patient was investigated. The combination of inductively coupled plasma mass spectrometry (ICP-MS), laser ablation (LA) ICP-MS for quantitative elemental bioimaging and hydrophilic interaction liquid chromatography (HILIC) ICP-MS for speciation analysis allowed to unambiguously diagnose the patient as a case of NSF. By means of ICP-MS, a total gadolinium concentration from 3.02 to 4.58 mg/kg was determined in the biopsy sample, indicating a considerable deposition of gadolinium in the patient's skin. LA-ICP-MS revealed a distinctly inhomogeneous distribution of gadolinium as well as concentrations of up to 400 mg/kg in individual sections of the skin biopsy. Furthermore, the correlation between the distributions of phosphorous and gadolinium indicates the presence of GdPO4 deposits in the tissue section. Speciation analysis by means of HILIC-ICP-MS showed the presence of the intact GBCA Gd-HP-DO3A eight years after the administration to the patient. The concentration of the contrast agent in the aqueous extract of the skin biopsy was found to be 1.76 nmol/L. Moreover, evidence for the presence of further highly polar gadolinium species in low concentrations was found.
    Analytical Chemistry 02/2015; 87(6). DOI:10.1021/ac504488k · 5.64 Impact Factor
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    ABSTRACT: Generation three, four, and five (G3, G4, and G5) poly(amidoamine) dendrimers were used for the encapsulation of palladium nanoparticles (Pd NPs) and their covalent anchoring within glass microreactors. G3-encapsulated Pd NPs showed the highest activity for a model Suzuki–Miyaura cross-coupling (SMC) reaction of the three different encapsulated Pd NPs tested, as compared to G4 and G5. A kinetic study indicated a role of the nanoparticle as a procatalyst, from which molecular species are formed with an induction time of approximately 1 min. The dendrimer–nanoparticle catalytic platform exhibited excellent reactivity (high turnover frequencies and numbers) compared to other Pd NP flow reactors and dendrimer-encapsulated Pd NPs at batch scale. Moreover, the Pd microreactor exhibited good stability, as witnessed by running the SMC reaction for more than 7 days with a low Pd leaching of 1.2 ppm. The covalently attached dendrimers may play a crucial role in stabilizing the Pd NPs, a critical feature in flow SMC reactions.
    ChemCatChem 02/2015; 7(6). DOI:10.1002/cctc.201500017 · 4.56 Impact Factor
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    Andreas Römpp · Uwe Karst ·
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    ABSTRACT: Mass spectrometry imaging provides spatial and molecular information for a wide range of analyte ions. The ability to map the distribution of biomolecules without labeling of target compounds has made imaging one of the most dynamic fields in mass spectrometry. In continuation of the ABC special issue “MALDI Imaging” in 2011 (Vol. 401, Issue 1), we cover recent trends in mass spectrometry imaging. The community has been very active and we have seen a number of exiting developments in instrumentation and applications. While MALDI is still the most widely used technique for mass spectrometry imaging, a number of alternative approaches, including ambient ionization sources, have been used increasingly in the last few years. In addition, sample preparation and data processing strategies have received increased interest in the MS imaging community. Sample preparation includes on-tissue chemistry, e.g., for digestion of proteins. This is related to a continuing shift away from imaging of (un ...
    Analytical and Bioanalytical Chemistry 02/2015; 407(8). DOI:10.1007/s00216-015-8479-7 · 3.44 Impact Factor

  • 02/2015; 3(1-4):57-58. DOI:10.1016/j.pisc.2014.11.019

Publication Stats

5k Citations
973.37 Total Impact Points


  • 1996-2015
    • University of Münster
      • Institute of Inorganic and Analytical Chemistry
      Muenster, North Rhine-Westphalia, Germany
  • 2004-2010
    • Universiteit Twente
      • Institute for Nanotechnology (MESA+)
      Enschede, Overijssel, Netherlands