Investigating drug metabolism with electrochemistry / mass spectrometry

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Investigating drug metabolism with electrochemistry / mass spectrometry
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Electrochemistry (EC) coupled to mass spectrometry (MS) in the last years has been proven to serve as a promising tool in the field of metabolism research. In conventional animal based metabolism studies, the identification of especially short living, reactive intermediates is difficult due to their binding to cell components such as proteins. With EC/MS as a purely instrumental approach, most oxidative metabolism reactions can be simulated. This way, it is possible to study the phase I metabolism of xenobiotics including the identification of reactive intermediates. By extending the setup and adding a solution of a biomolecule like a peptide, protein or DNA immediately after EC oxidation, the phase II metabolism can be studied and toxicity assessment can be performed as well.
Keywords biochemistry methods
Hematite Karst Combine harvester Munster, Haut-Rhin Hyperpolarisierung Chemical compound Metabolism Mass spectrometry River source Wine tasting descriptors Chemistry
Analgesic Toxicity Paracetamol Separation process Paracetamol Metabolite Munster, Haut-Rhin Recreational drug use Headache Oxide
Paracetamol Metabolite Intergranular corrosion Arzneimitteldosis
Metabolite Functional group Radiation damage Lactitol Cell (biology) Protein Wursthülle Electronic cigarette
Chemical experiment
Übergangszustand Golgi apparatus Munster, Haut-Rhin Chemical experiment Action potential Ocean current Wine tasting descriptors Klinisches Experiment Combine harvester Soft matter Cell (biology) Mass spectrometry Ausgangsgestein Chemist Oxide
Paracetamol Combine harvester Metabolite Mass spectrometry Chemistry
Toxicity Species Fire Peptide Battery (electricity) Protein
Deterrence (legal) Systemic therapy Peptide Chromatography Chemical experiment Chemical property Solution Chemical reaction Chemist Capillary electrophoresis
Setzen <Verfahrenstechnik> Recreational drug use Chemical experiment Growth medium Chemical compound
Mastic (plant resin) Adduct Paracetamol Munster, Haut-Rhin Recreational drug use Peptide Chromatography Growth medium Chemistry Protein Enzyme Azo coupling Protein Protein Elektronentransfer Arzneimittelforschung Process (computing)
Nuclear magnetic resonance Bisacodyl Functional group Cell (biology) Chemical structure Ion channel Potato chip Oxide
the oxidative metabolise most one of the major the friends of strategies of the human body the so-called you know biotics compounds which into the body but any anthropogenic source are converted into products have higher polarity which can be in then be easy excrete it by the kidneys and the u.a.e. to study the metabolic reactions in the body.
his of different analytical methods has been implemented they are based on in vitro own visual systems and our approach is the combination between electric chemistry and mass spectrometry which is purely instrumental this way any influence from the biological nature sees can be avoided.
a typical example for that is paracetamol one of the most commonly used drugs in the world. paracetamol isn't over the counter drugs which is widely used as a painkiller for example for the relief of headache it is known that paracetamol can cause severe liver damage when an overdose is taken responsible for the toxic effects is a reactive metabolite which is formed you to enzymatic oxidation in the liver.
this metabolite this called map he usually when taking paracetamol and recommended doses this metabolite is detoxify by two to sign which the tripartite highly abundant in the liver when taking an overdose of paracetamol the metabolite occurs and higher amounts and therefore can cost the depletion of two to find and the liver and in this.
case the metabolite can also buy into other biomolecules form for example important function of proteins which ultimately leads to throw cell damage or sell just function or. this is an electrochemical felt that what you like show it can be made from different cameo which shows an independent of the end of life that should be able to guide.
i apply a potential to be like for chemical cell which is controlled by a homemade potential said oxidation takes place. the f.b.i. and off the electric chemical cell is directed transferred into the mastectomy to wear detection takes place there by it is important to keep the transition time between the electorate chemicals found in a mass spectrometer as soft as possible in order to allow the detection of even shortlist reactive intermediates.
the first experiments differently apply important for him to select committee also want to warn parents of all church and current progress as one who taught at the same time aspect trial reported by combines to date asserts so-called last autumn rounds can be up to last autumn runs on general hospital which have to look into certain mention the.
and until the plight of today shouldn't you can season last quarter of a possible in total two signals can be seen one showing in decreasing signal intensity which can be traced back to his electrochemical oxidation of persuadable the other sick no shows an increase in secular intensity cost was a generational selective metabolite not the.
this is also the major benefit of electro chemistry combined with mass spectrometry whether this possible to detect reactive metabolites which would normally buy into the biological metrics president to be two hundred people sellable not say advantage of electric a mystery combination is not spectrometry is a possibility of performing binding studies of.
reactive species by adding a look at the fires are just peptides proteins all d.n.a. to their foot off the electrical cell was as possible toxic side effects can be identified.
for the exhumation with biomolecules the instrumental said that needs to be modified slightly. the second tyrant containing a solution a peptide property in our d.n.a. is directly connected to the efforts of the electro chemicals help.
not to specific reaction time with defined by the length of capillary give a direct payments to take some can be performed or a liquid chromatography system can be integrated between the electorate chemical sales and a mastectomy through in order to separate the different factions have had problems similar to previously reported result.
old for the notes also identified by means of most appropriate to do work for we applied for the network formation studies have shown you don't want to fight for you can be integrated with a lectern committed to the drug compounds and react differently media to conform for the mailbox was a major problem in addition to that and then submitted guy just can be performed.
the resulting into medicare flights can be separated by means of liquid chromatography and identified by means of high resolution most are from a tree was this is a binding side of the reactive into media it is a protein can be identified.
the representative example of paracetamol demonstrates were well the benefits of electro chemistry couple to must pick from a tree general conclusion is not allowed because only one electron transfer process this can be mimicked well with this beauty in some mental approach critical drug candidates can be identified early in drug development because intermediates can be identified.
incorrect trust with this resources and money can be saved.
technical improvements and ongoing research in our group but also in collaborations focus on miniaturization and also an upscaling micro fleet devices are used to shorten the time between oxidation a mastectomy to protection and with this we can investigate highly reactive intermediates. upscaling is used to elucidate the structure in more detail for example with nuclear magnetic resonance.