European Virtual Institute for Speciation Analysis EVISA

Bad Münster am Stein-Ebernburg, Germany

European Virtual Institute for Speciation Analysis EVISA

Bad Münster am Stein-Ebernburg, Germany

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Birka M.,University of Munster | Wentker K.S.,University of Munster | Lusmoller E.,Johannes Wesling Klinikum Minden | Arheilger B.,Johannes Wesling Klinikum Minden | And 5 more authors.
Analytical Chemistry | Year: 2015

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 sample 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 one 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 phosphorus and gadolinium suggests 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. (Figure Presented). © 2015 American Chemical Society.


Meermann B.,University of Munster | Meermann B.,Federal Institute of Hydrology | Sperling M.,University of Munster | Sperling M.,European Virtual Institute for Speciation Analysis EVISA
Analytical and Bioanalytical Chemistry | Year: 2012

Method development and applications of hyphenated techniques as tools for speciation analysis of metalbased pharmaceuticals are summarized within this review. Advantages and limitations of the separation modes-highperformance liquid chromatography (HPLC), capillary electrophoresis (CE), and gas chromatography (GC)-as well as the detection modes-inductively coupled plasma-mass spectrometry (ICP-MS) and electrospray ionization-mass spectrometry (ESI-MS)-are discussed. ICP-MS detection is found to be advantageous for the quantification of drugs containing metals and other heteroatoms. The species-independent sensitivity and multielement capabilities of ICP-MS allow it to be used for quantification even when species-specific standards are not available, as well as to determine the stoichiometry in metallodrug-biomolecule interactions. Molecular information that is totally destroyed when ICP is applied as ionization source and is therefore not obtainable via ICP-MS detection can be accessed by the complementary technique of ESI-MS. Speciation analysis combining both elemental and molecular information is therefore a powerful tool for the analysis of metal-based pharmaceuticals and their metabolites in body fluids and other relevant matrices. © Springer-Verlag 2012.


Reifschneider O.,University of Munster | Wehe C.A.,University of Munster | Raj I.,University of Munster | Ehmcke J.,University of Munster | And 4 more authors.
Metallomics | Year: 2013

A novel quantification approach for tissue imaging using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) based on tissue embedding in cold-curing resins (Technovit 7100) is presented. With respect to massive side effects on cisplatin, the platinum distribution at different time intervals after cisplatin treatment of mice was determined quantitatively in different tissues including cochlea, testis and kidney. For this purpose, cold-curing resin blocks spiked with different amounts of platinum acetyl acetonate prior to curing were ablated after sectioning at 5 μm thickness and were analysed using ICP-MS after microwave digestion. High spatial resolution and limits of detection in the low ppb range (8 μg kg -1) were achieved using a simple and efficient sample preparation. External calibration using the Technovit 7100 standards proved to yield precise and reproducible quantification results. The distribution and retention behaviour of cisplatin in the organs was investigated using the new calibration method. © 2013 The Royal Society of Chemistry.


Telgmann L.,University of Munster | Faber H.,University of Munster | Jahn S.,University of Munster | Melles D.,University of Munster | And 4 more authors.
Journal of Chromatography A | Year: 2012

Oxidative and potentially metabolic pathways of the five most frequently used contrast agents for magnetic resonance imaging (MRI) based on gadolinium (Gd) are examined. The oxidation of gadopentetate (Gd-DTPA) was studied with a focus on electrochemical oxidation coupled to analytical separation methods and mass spectrometric detection. Mass voltammograms generated with online electrochemistry/electrospray ionization mass spectrometry (EC/ESI-MS) gave a first overview of oxidation products. Two potential metabolites could be detected, with the major metabolite originating from an . N-dealkylation (. M1). Four other Gd complexes used as MRI contrast agents showed similar reactions in the EC/ESI-MS set-up. To obtain more information about the properties and the quantity of the generated products, a wide range of separation and detection techniques was applied in further experiments. Gd-DTPA and its . N-dealkylation product were successfully separated by capillary electrophoresis (CE) and detected by ESI-MS and inductively coupled plasma (ICP)-MS, respectively. CE experiments indicated that the second oxidation product (. M2) detected in the mass voltammogram is unstable and decomposes to . M1. Employing EC/CE/ICP-MS, the quantification of the metabolites could be achieved. Under the employed conditions, 8.8% of Gd-DTPA was oxidized. Online experiments with high performance liquid chromatography (HPLC) coupled to ESI-MS confirmed the decomposition of . M2. Time-resolved measurements showed a decrease of . M2 and a simultaneous increase in . M1 within only a few minutes, confirming the conclusion that . M2 degrades to . M1, while EC/LC/ICP-MS measurements provided quantitative evidence as well. The EC/MS simulation shows that a metabolic transformation should not be disregarded in further research regarding the trigger of nephrogenic systemic fibrosis (NSF), a disease exclusively observed for several hundred dialysis patients after delivery of Gd-based MRI contrast agents with linear structure. Furthermore, the used methods may allow the prediction of options for the oxidative removal of these contrast agents from wastewaters. © 2012 Elsevier B.V.


Niehaus R.,University of Munster | Sperling M.,University of Munster | Sperling M.,European Virtual Institute for Speciation Analysis EVISA | Karst U.,University of Munster
Journal of Analytical Atomic Spectrometry | Year: 2015

A 213 nm 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 inserted in-line between the LA and the ICP-MS, while helium served as carrier gas for material transport. A considerably larger number of particles above 0.3 μm 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 (i.e. Ti and V) for varying laser fluences. The results indicate a strong deviation of up to 20% from the expected 51V/48Ti ratio for laser fluences close to the threshold for ablation. © The Royal Society of Chemistry 2015.


Brauckmann C.,University of Munster | Wehe C.A.,University of Munster | Kieshauer M.,University of Munster | Lanvers-Kaminsky C.,University of Munster | And 3 more authors.
Analytical and Bioanalytical Chemistry | Year: 2013

This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like β-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin. LGA was selected as the model protein in addition to the two most abundant blood proteins HSA and HB. In case of the model protein, the effect of free thiol groups on the affinity of cisplatin, carboplatin, and oxaliplatin was investigated by means of liquid chromatography electrospray ionization time-of-flight mass spectrometry (LC/ESI-ToF-MS). The reduced form of LGA, which contains four free thiol groups more than the native LGA, shows a much higher affinity to the platinum-based drugs. By means of liquid chromatography coupled to inductively coupled plasma mass spectrometry, the reaction behavior of the platinum-based drugs towards HSA and HB was investigated under different conditions considering the chloride concentration (4 or 100 mM) and the incubation time (24 and 48 h). In case of carboplatin, less than 6 % protein-bound platinum was detected. However, both cisplatin and oxaliplatin display a high affinity to the proteins investigated. Further information was obtained by means of LC/ESI-ToF-MS. In case of oxaliplatin, the complex [Pt(DACH)]2+ (DACH = C6N 2H14) was identified interacting with HSA and HB. For cisplatin, different results were observed for the two proteins. The complex [Pt(NH3)2Cl]+ interacted predominantly with HSA and [Pt(NH3)2]2+ with HB. [Figure not available: see fulltext.] © 2012 Springer-Verlag.


Telgmann L.,University of Munster | Sperling M.,University of Munster | Sperling M.,European Virtual Institute for Speciation Analysis EVISA | Karst U.,University of Munster
Analytica Chimica Acta | Year: 2013

The development of analytical methods and strategies to determine gadolinium and its complexes in biological and environmental matrices is evaluated in this review.Gadolinium (Gd) chelates are employed as contrast agents for magnetic resonance imaging (MRI) since the 1980s. In general they were considered as safe and well-tolerated, when in 2006, the disease nephrogenic systemic fibrosis (NSF) was connected to the administration of MRI contrast agents based on Gd. Pathogenesis and etiology of NSF are yet unclear and called for the development of several analytical methods to obtain elucidation in this field. Determination of Gd complex stability in vitro and in vivo, as well as the quantification of Gd in body fluids like blood and urine was carried out. Separation of the Gd chelates was achieved with high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). For detection, various methods were employed, including UV-vis absorbance and fluorescence spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and inductively coupled plasma mass spectrometry (ICP-MS).A second challenge for analysts was the discovery of high concentrations of anthropogenic Gd in surface waters draining populated areas. The source could soon be determined to be the increasing administration of Gd complexes during MRI examinations. Identification and quantification of the contrast agents was carried out in various surface and groundwater samples to determine the behavior and fate of the Gd chelates in the environment. The improvement of limits of detection (LOD) and limits of quantification (LOQ) was and still is the goal of past and ongoing projects. © 2012 Elsevier B.V.


Holtkamp M.,University of Munster | Elseberg T.,University of Munster | Wehe C.A.,University of Munster | Sperling M.,University of Munster | And 2 more authors.
Journal of Analytical Atomic Spectrometry | Year: 2013

A thorough investigation of strategies to overcome the effect of mercury losses during TXRF analysis was carried out. The vaporisation of mercury on sampling targets, associated with too low concentrations determined, depends on the nature of the respective Hg species and the dwell time of the analytes on the target. To prevent vaporisation, oxidation with ammonium persulfate and complexation with ethylenediamine tetraacetate (EDTA) and dimercaptosuccinic acid (DMSA) were investigated. Whereas both approaches were effective in reducing the Hg losses by vaporisation, the complexation approaches turned out to be particularly efficient. Both EDTA and DMSA retain the different mercury species quantitatively over several hours. Based on this approach, a method for mercury determination by TXRF in liquid samples was developed, successfully validated by inductively coupled plasma optical emission spectrometry and applied to the analysis of a mercury-containing vaccine sample. This journal is © The Royal Society of Chemistry.


Birka M.,University of Munster | Wehe C.A.,University of Munster | Telgmann L.,University of Munster | Sperling M.,University of Munster | And 2 more authors.
Journal of Chromatography A | Year: 2013

The application of gadolinium(Gd)-based contrast agents to support medical examinations by magnetic resonance imaging (MRI) results in a large input of Gd into the environment. The long-term effects of the anthropogenic Gd anomaly, especially on aqueous ecosystems, are mostly unknown. The identification and quantification of Gd-based contrast agents in the aquatic environment requires the use of powerful methods of speciation analysis. Therefore, a method employing the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and inductively coupled plasma sector field mass spectrometry (ICP-SFMS) with sample introduction as dry aerosol generated by desolvation was developed. The desolvation resulted in improved limits of detection for the predominantly used contrast agents well below 0.10. nmol/L. This method was subsequently used for the analysis of Gd species in surface waters. Samples from a nature reserve in the city of Münster (Germany), into which the effluent from the city's main wastewater treatment plant enters the environment, were examined. The contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were identified and quantified in constant ratios in those samples. The concentrations were found in a range from 0.59. nmol/L for Gd-DOTA up to 3.55. nmol/L for Gd-BT-DO3A. As a result of mass balancing, the contrast agent concentration was found to account for 74-89% of total Gd concentrations, possibly indicating the presence of further Gd species. Nevertheless, there was no direct indication of species transformation by transmetallation reactions resulting in such Gd species. The determination of REE patterns by means of ICP-MS confirmed the results of speciation analysis showing significant Gd anomalies. © 2013 Elsevier B.V.


Blaske F.,University of Munster | Reifschneider O.,University of Munster | Gosheger G.,University of Munster | Wehe C.A.,University of Munster | And 5 more authors.
Analytical Chemistry | Year: 2014

The distribution of different chemical elements from a nanosilver-coated bone implant was visualized, combining the benefits of two complementary methods for elemental bioimaging, the nondestructive micro X-ray fluorescence (μ-XRF), and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Challenges caused by the physically inhomogeneous materials including bone and soft tissues were addressed by polymer embedding. With the use of μ-XRF, fast sample mapping was achieved obtaining titanium and vanadium signals from the metal implant as well as phosphorus and calcium signals representing hard bone tissue and sulfur distribution representing soft tissues. Only by the use of LA-ICP-MS, the required high sensitivity and low detection limits for the determination of silver were obtained. Metal distribution within the part of cancellous bone was revealed for silver as well as for the implant constituents titanium, vanadium, and aluminum. Furthermore, the detection of coinciding high local zirconium and aluminum signals at the implant surface indicates remaining blasting abrasive from preoperative surface treatment of the nanosilver-coated device. © 2013 American Chemical Society.

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