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Bad Münster am Stein-Ebernburg, Germany

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 | Wehe C.A.,University of Munster | Kunnemeyer J.,University of Munster | Bulter A.-C.,University of Munster | And 3 more authors.
Analytical and Bioanalytical Chemistry | Year: 2012

The risk of transmetalation reactions between gadolinium complexes used as contrast agents for magnetic resonance imaging (MRI) and iron ions is examined under physiological conditions. A fast separation of gadopentetate (Gd-DTPA) and gadoterate (Gd-DOTA) and the respective Fe transmetalation products was accomplished by highperformance liquid chromatography. For detection, the LC system was coupled to an Orbitrap electrospray ionization mass spectrometer to achieve a detection limit as low as 50 nmol/L for Fe-DTPA. In vitro experiments revealed the formation of Fe-DTPA in blood plasma samples with Gd- DTPA and Fe(III) citrate. Analysis after different incubation times of the sample showed that the exchange of the metal ions is significantly dependent on time. If this reaction takes place in the body of MRI patients, this could explain why the disease nephrogenic systemic fibrosis (NSF) develops only after a longer retention of the linear Gd complex in the patient's body. Transmetalation either with endogenous Fe (II)/Fe(III) ions or with parenteral Fe supplements with Gd- DTPA could not be proven under the applied conditions. The high stability of Gd-DOTA is responsible that transmetalation between this macrocylic complex and neither of the Fe species was observed. These findings are important because NSF only develops after administration of Gd complexes with linear ligands. The results indicate that transmetalation reactions may be a trigger for the development of NSF, if free Fe(III) ions are accessible during a prolonged dwell time of Gd complexes with linear ligands in the patient's body. © Springer-Verlag 2012.

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.

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.

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