Bettina Seiwert - Academia.edu (original) (raw)

Papers by Bettina Seiwert

Archives of Toxicology

Lycorine is the main alkaloid of many Amaryllidaceae and known to cause poisoning with still unkn... more Lycorine is the main alkaloid of many Amaryllidaceae and known to cause poisoning with still unknown mechanisms. Longer lasting toxicological core symptoms of nausea and emesis may become a burden for human and animal patients and may result in substantial loss of water and electrolytes. To optimise the only empirical symptomatic antiemetic drug treatment at present, it is important to elucidate the causative involved targets of lycorine-induced emesis. Therefore, in the current study, we have tested the actions of a various antiemetic drugs with selective receptor affinities on lycorine-induced nausea and emesis in vivo in dogs. Beagle dogs were pre-treated in a saline vehicle-controlled crossover and random design with diphenhydramine, maropitant, metoclopramide, ondansetron or scopolamine prior lycorine administration (2 mg/kg subcutaneously). In vivo effects were assessed by a scoring system for nausea and emesis as well as by the number and lag time of emetic events for at least 3 h. Moreover, plasma pharmacokinetic analysis was carried out for ondansetron before and after lycorine injection. The data show that histaminergic (H1), muscarinic and dopaminergic (D2) receptors are presumably not involved in lycorine-induced emetic effects. While ondansetron significantly reduced the number of emetic events, lycorine-induced emesis was completely blocked by maropitant. Only ondansetron also significantly decreased the level of nausea and was able to prolong the lag time until onset of emesis suggesting a preferential participation of 5-HT3 receptors in lycorine-induced nausea. Thus, it is the first in vivo report evidencing that predominantly neurokinin-1 (NK1) and to a lesser extent 5-hydroxytryptamine 3 (5-HT3) receptors are involved in lycorine-induced emesis facilitating a target-oriented therapy.

Toxicon, 2011

Ingestions of plant material from Amaryllidaceae, especially the bulbs of daffodils, are known to... more Ingestions of plant material from Amaryllidaceae, especially the bulbs of daffodils, are known to be toxic, representing a persistent cause of poisoning in human and animals. Empiric data from case reports suggested, that the alkaloid lycorine could be the toxic constituent of the multi-component mixture responsible for symptoms like nausea and emesis. Systematic studies of the in vivo effects of the amaryllidaceaeous-type alkaloids are not available. Therefore, in an open, prospective, randomized and controlled trial we studied the dose–effect relationship of lycorine-induced nausea and emesis and the toxicokinetics of lycorine in beagle dogs. Subcutaneously administered lycorine-induced nausea and emesis starting at 0.5 mg/kg body weight reaching statistical significance at 1.0 mg/kg. The maximum emetic dose of lycorine (ED100) was 2 mg/kg body weight. There was a correlation between dose and nausea score as well as between dose and number of the induced emetic events. Nausea and emesis were short-lasting and occurred not later than 2.5 h post dose. Lycorine showed linear plasma kinetics with a mean elimination half-life of 0.67 and 0.3 h after single s.c. and i.v. administration, compatible with the clinical course of nausea and emesis. The mean oral bioavailability was calculated to be about 40%. Biochemical and haematological parameters of safety showed no pathological signs. The results provide evidence that lycorine can be considered as a main, if not the crucial constituent responsible for nausea and emesis in human and animals in poisoning due to ingestion of plant material of the Amaryllidaceae.

Analytical and Bioanalytical Chemistry, 2007

N-(2-Ferroceneethyl)maleimide (FEM) is introduced as an electroactive derivatizing agent for thio... more N-(2-Ferroceneethyl)maleimide (FEM) is introduced as an electroactive derivatizing agent for thiol functionalities in proteins. Using appropriate reaction conditions, the derivatization is completed within five minutes and no unspecific labeling of free amino functions is observed. Liquid chromatography/electrochemistry/mass spectrometry was used to detect the reaction products. The reagent is a useful tool for determining the number of free thiol groups or the total number of free and disulfide-bound thiol groups in proteins. The electrochemical cell provides additional information, because the increase in mass spectrometric response upon electrochemical oxidation of the neutral ferrocene to the charged ferrocinium groups is monitored. The method was successfully applied to the analysis of native proteins and their tryptic digests.

Analytical and Bioanalytical Chemistry, 2008

Ferrocene-based derivatization has raised considerable interest in many fields of analytical chem... more Ferrocene-based derivatization has raised considerable interest in many fields of analytical chemistry. This is due to the well-established chemistry of ferrocenes, which allows rapid and easy access to a large number of reagents and derivatives. Furthermore, the electrochemical properties of ferrocenes are attractive with respect to their detection. This paper summarizes the available reagents, the reaction conditions and the different approaches for detection. While electrochemical detection is still most widely used to detect ferrocene derivatives, e.g., in the field of DNA analysis, the emerging combination of analytical separation methods with electrochemistry, mass spectrometry and atomic spectroscopy allows ferrocenes to be applied more universally and in novel applications where strongly improved selectivity and limits of detection are required.

Nachrichten Aus Der Chemie, 2005

Elektrochemie erweitert das Einsatzgebiet der LC/MS auch auf unpolare oder nur schwer ionisierbar... more Elektrochemie erweitert das Einsatzgebiet der LC/MS auch auf unpolare oder nur schwer ionisierbare Verbindungen. Eine coulometrische Zelle zwischen Trennsäule und MS eignet sich sowohl zur Nachsäulenderivatisierung als auch zur Untersuchung von Redoxprozessen.

Journal of The American Society for Mass Spectrometry, 2004

Ferrocenoyl piperazide is introduced as a new pre-column derivatizing agent for the analysis of v... more Ferrocenoyl piperazide is introduced as a new pre-column derivatizing agent for the analysis of various isocyanates in air samples using reversed-phase liquid chromatographic separation, electrochemical oxidation/ionization, and mass spectrometry. The nonpolar derivatives can be separated well using a phenyl-modified stationary phase and a formic acid/ammonium formate buffer of pH 3, which yields excellent separations, especially for one problematic group of isocyanates consisting of 2,4- and 2,6-toluylenediisocyanate (2,4- and 2,6-TDI) and hexamethylenediisocyanate (HDI). Electrochemical oxidation at low potentials (0. 5 V versus Pd/H2) leads to formation of charged products, which are nebulized in a commercial atmospheric pressure chemical ionization (APCI) source, with the corona discharge operated only at low voltage. Limits of detection between 6 and 20 nmol/L are obtained for the isocyanate derivatives, and calibration is linear over at least two decades of concentration. The method is applied for the analysis of air after thermal degradation of a polyurethane foam, and it is demonstrated that it is suitable as well for the analysis of carboxylic acid chlorides and of isothiocyanates.

Journal of The American Society for Mass Spectrometry, 2008

A method for the simultaneous determination of the number of free cysteine groups and disulfide-b... more A method for the simultaneous determination of the number of free cysteine groups and disulfide-bound cysteine groups in proteins has been developed based on the sequential labeling of free and bound thiol functionalities with two ferrocene-based maleimide reagents. Liquid chromatography/electrochemistry/mass spectrometry was used to assign the N-(2-ferroceneethyl)maleimide (FEM) labeled free cysteine functionalities in a tryptic digest mixture, whereas a precursor ion scan enables the detection of peptides with ferrocenecarboxylic acid-(2-maleimidoyl)ethylamide (FMEA) labeled disulfide-bound cysteine groups after reduction. Fragment spectra of the labeled peptides yield an excellent coverage of b-type and y-type ions. The ferrocene labeled cysteines were fragmented as 412 Da (FEM) and 455 Da (FMEA). These fragment masses are significantly higher than unlabeled amino acids or dipeptides and are easily detected. The position of free and disulfide-bound cysteine may therefore be assigned in an amino acid sequence.

Analytical Chemistry, 2007

Analytical and Bioanalytical Chemistry, 2009

A liquid chromatography (LC)/mass spectrometry method was developed for the determination of sele... more A liquid chromatography (LC)/mass spectrometry method was developed for the determination of selected biogenic amines in various fish and other food samples. It is based on a precolumn derivatization of the amines with succinimidylferrocenyl propionate under formation of the respective amides and their reversed-phase liquid-chromatographic separation with subsequent electrospray ionization mass-spectrometric detection. Deuterated putescine, cadaverine, and histamine are added prior to the derivatization as internal standards that are coeluted, thus allowing excellent reproducibility of the analysis to be achieved. Depending on the analyte, the limits of detection were between 1.2 and 19.0 mg/kg, covering between 2 and 3 decades of linearity. The limit of detection and the linear range for histamine are suitable for the surveillance of the only defined European threshold for biogenic amines in fish samples. Compared with the established ortho-phthalaldehyde (OPA)/LC/fluorescence method, the newly developed method allows an unambiguous identification of the biogenic amines by their mass spectra in addition to only retention times, a fivefold acceleration of the separation, and independency from the sample matrix owing to the isotope-labeled internal standards. Various fish, calamari, and salami samples were successfully analyzed with the new method and validated with an independent OPA/LC/fluorescence method.

Organic & Biomolecular Chemistry, 2005

Analytical Chemistry, 2009

Giavalisco, P.; Hummel, J.; Lisec, J.; Inostroza, A. C.; Catchpole, G.; Willmitzer, L. Anal. ... more 10) Giavalisco, P.; Hummel, J.; Lisec, J.; Inostroza, A. C.; Catchpole, G.; Willmitzer, L. Anal. Chem. 2008, 80, 9417-9425.

The analysis of lipids is technically very challenging, not only due to the large number of vario... more The analysis of lipids is technically very challenging, not only due to the large number of various classes of compounds provided by the cell, but also due to the enormous heterogeneity of these various classes. Especially plants with their large pigment content and their high degree of polyunsaturated acyl residues make lipid analysis in this system even more complicated. Due to this high complexity, more and more sophisticated large-scale lipid-analysis systems have been developed, intended for the analysis of the so-called “lipidome”, that is the entire lipid composition of a cell or a whole organism. These methods often consist of various building blocks, which show interlaced modularity. The two basic elements of a lipidomic analysis are an efficient extraction procedure and a sensitive detection system. In addition to these two basic elements, depending on the analytical question, additional separation and sample purification procedures can be introduced. Mass spectrometry (MS)-based techniques are at the forefront of lipidomic analysis. These extremely sensitive and accurate detection methods are applied to investigate all kinds of lipid. Their application, in combination with various plant-specific techniques of extraction and separation, including solid-phase extraction, thin-layer chromatography and high-performance liquid chromatography are presented in this chapter. Most of the MS-based technologies for lipid profiling of partially polar lipids rely on electrospray ionization, while more apolar lipids, like sterols, can be ionized by techniques, such as atmospheric pressure chemical ionization. A number of various applications employing these mass spectrometric methods will be discussed. Finally combinations of various separation and detection technologies, so-called hyphenated approaches, such as high-performance liquid chromatography coupled to mass spectrometry or gas chromatography coupled to time of flight or quad-rupole mass spectrometry, are introduced and their suitability for lipid analysis are discussed.