Steen Honoré Hansen 
Professor 
E-mail: shh(at)farma.ku.dk  
Telefon: 35 33 62 56
Rum: 13/619

Correlation between the formation of glutathione-conjugates and cytotoxicity.
The metabolism of a number of drug substances (e.g. diclofenac, troglitazone, nifedipine, etc) can result in formation of glutathione-conjugates (SG-conjugates). Such conjugates are often used as indicators of the formation of reactive drug metabolites in vitro and in vivo. The research group for drug metabolism and analytical chemistry has for many years been investigating the formation of reactive drug metabolites, and has among other thing focus on the correlation between the aount of SG-conjugates formed and cytotoxicity.  The present project involve the establishment of assays for cytotoxicity in cell cultures and in sub-cellular models as well as identification and measurement og SG-conjugates formed in in vitro and/or in vivo model systems.
The research project will involve work with cell models (tytpically hepatocytes) and analytical chemical techniques (HPLC, MS and NMR).
Supervisors:  Steen Honoré Hansen
No of students: 1-2

Direct analysis of compounds on TLC plates
Thin layer chromatography (TLC) is still a widely used analytical technique in organic synthesis as well as in natural product chemistry. Principally, it provides information about the number of components in a mixture, and identification can – if needed – be performed by comparison of the retention factors as in other kinds of chromatography. Using a relatively new technique in mass spectrometry, Desorption Electrospray Ionization, it is possible to analyze compounds directly on surfaces by spraying the surface with a narrow beam of solvent, thereby obtaining an unambiguous identification of the compound on the surface. In this project DESI-MS will be further developed and used for analysis of TLC plates, possibly in collaboration with synthesis chemists or natural product chemists.
Supervisors: Christian Janfelt and Steen Honoré Hansen
Maximum number of students: 1
 
 

Analysis of wine
Denmark has now been a wine-producing country for a number of years and the country holds a wine quota in EU. Similar to requirements for other food products or drugs it is important to obtain a better knowledge about the manufacturing process as well as of the final product.
A number of health promoting as well as more or less toxic substances can be present in wine. A number of modern analytical chemical techniques are available for the characterisation of grapes as well as of the produces wine.
Analytical chemical methods for the analysis of specified components in wine should be developed. The developed methods should then be used for comparison of wine produced in Denmark of grapes grown in Denmark and samples of foreign wine.
Supervisor: Steen Honoré Hansen
No of students: 1-2

Analysis of endogenous morphine
Reports of morphine (and codeine) being an endogenously formed compound have appeared during the last years and the substances have been detected in brain homogenates from humans. Thus a number of scientific papers point in the direction that morphine may be a common transmitter in the CNS in mammals.
However, it is a question of very low concentrations for which very sensitive analytical chemical methods are required in order to be measured quantatively. This is probably why so few reports have been published until now. There is little knowledge about the function an endogenous level of morphine may have, and what impact further knowledge in this area may have on CNS-research.
In this project sensitive analytical chemical techniques/methods for the assay of morphine in biological samples should be developed.
Supervisors:  Steen Honoré Hansen
No of students: 1-2

Reactivity between drug substance and excipients
Investigations have shown that impurities in drug preparations may be formed due to reactions between the drug substance and an excipient. Citric acid, glycerol, polyethylenglycol are among the excipient known to react with some drug substances. Citric acid can react with amines and alcohols while glycerol can react with carboxylic acid. In some oral solutions of drug substances citric acid, glycerol and sorbic acid are present simultaneously. Reactions taking place and impurities formed in an oral solution should be investigated in detail using modern analytical chemical techniques (HPLC, GC, CE, LC-MS and NMR).
Supervisor: Steen Honoré Hansen
No of students: 1-2

Mitochondrial effects of drug compounds.
The mitochondria are the cellular ‘energy’ plants’ and as such play an important role in cellular functionality and viability. In the course of drug-induced cellular toxicity, the mitochondria often become involved at some stage, which may lead to either cellular apoptosis (controlled cell-death) or necrosis. Several mechanisms may cause the involvement of the mitochondria in drug-induced cellular toxicity, but it seems likely that drug metabolism plays a role in these toxicities. As part of the research concerning chemically reactive drug metabolites, it is desired to investigate the effects on mitochondria by selected drug compounds and their metabolites.
The project may include work with both sub-cellular fractions as well as whole-cell system. In addition there will be opportunities to work with more advanced analytical instrumentation, e.g. HPLC-MS and HPLC-MS/MS. For suitable candidates, collaboration and studies with research groups in the US or England will be possible.
Supervisor: Christian Skonberg or Steen Honore Hansen.
Max. Number of students: 2
  

Imaging of compounds in plant tissue
 Using a new technique with mass spectrometry, Desorption Electrospray Ionization Imaging, it is possible to image the distribution of compounds on a surface. The sample is scanned line by line while mass spectra are recorded in every single point on the surface. Subsequently, for every point on the surface information about the signal intensity from a specific compound may be retrieved and used to generate a map showing where on the surface the compound is present.
In this project the technique will be used to analyze the distribution of compounds in plants. The project will be planned in collaboration with natural product chemists and focused on one or two plants which will be characterized further.
Supervisors: Christian Janfelt and Steen Honoré Hansen
Maximum number of students: 1

 Imaging of drugs in tissue sections from mice
Using a new technique with mass spectrometry, Desorption Electrospray Ionization Imaging (DESI-MS), it is possible to image the distribution of compounds on a surface. It this way, we can follow a drug dosed to a mouse, creating images of the mouse that show where in the body the drug goes, and how it is metabolized.
In this project a mouse will be dosed with a drug, and subsequently the brain, liver and kidney of the mouse will be cut in thin slices which are then analyzed with DESI-MS. The aim of the project is to image where the drug goes and in which doses we can see the drug and its metabolites.
Supervisors: Christian Janfelt and Steen Honoré Hansen.
Maximum number of students: 1