Electrochemical side reactions, often referred to as "electrode fouling", are known to be a major challenge in electro-organic synthesis and the functionality of modern batteries. Often, polymerization of one or more components is observed. When reaching their limit of solubility, those polymers tend to adsorb on the surface of the electrode, resulting in a passivation of the respective electrode area, which may impact electrochemical performance. Here, matrixassisted laser-desorption/ionization mass spectrometry (MALDI-MS) is presented as valuable imaging technique to visualize polymer deposition on electrode surfaces. Oligomer size distribution and its dependency on the contact time were imaged on a boron-doped diamond (BDD) anode of an electrochemical flow-through cell. The approach allows to detect weak spots, where electrode fouling may take place and provides insight into the identity of side-product pathways.
Trapped ion mobility spectrometry (TIMS) is presented
as a new
and rapid method to distinguish between electrochemically generated
isomeric oxidation products. Separation was performed online directly
after generation and ionization of the analytes, thus providing the
opportunity to detect even short-lived and reactive transformation
products. The same setup enables structure elucidation based on TIMS
aligned fragmentation experiments. Due to the high resolution, TIMS
was able to distinguish between two isomeric transformation products
of the model compound metoprolol, which only differ in the position
of the hydroxylation taking place in the benzylic and aromatic positions,
respectively. Using this method, the analysis time is at least five
times shorter compared to conventional chromatography approaches.
Consequently, TIMS may arise as a powerful tool in electrochemical
metabolism studies.
In drug development, metabolite standards of new chemical entities are required for a comprehensive safety evaluation. Stable isotope-labeled internal metabolite standards at the milligram scale, which are difficult and expensive to synthesize in common bottom-up approaches, are necessary for metabolite quantification using liquid chromatography/mass spectrometry. A preparative electrochemical flowthrough cell is presented here as a powerful tool for the cheap and straightforward synthesis of milligram amounts of isotopically labeled metabolite standards. The developed cell scales up established, so-called "coulometric" electrochemical cells.Problems like electrode fouling and cross contamination between syntheses are addressed by the use of exchangeable working electrodes. The applicability of the developed cell for the synthesis of metabolite standards is demonstrated using isotopically labeled acetaminophen as a model system for the generation of a biologically relevant phase II metabolite.
Electrochemical side reactions, often referred to as "electrode fouling", are known to be a major challenge in electro-organic synthesis and the functionality of modern batteries. Often, polymerization of one or more components is observed. When reaching their limit of solubility, those polymers tend to adsorb on the surface of the electrode, resulting in a passivation of the respective electrode area, which may impact electrochemical performance. Here, matrixassisted laser-desorption/ionization mass spectrometry (MALDI-MS) is presented as valuable imaging technique to visualize polymer deposition on electrode surfaces. Oligomer size distribution and its dependency on the contact time were imaged on a boron-doped diamond (BDD) anode of an electrochemical flow-through cell. The approach allows to detect weak spots, where electrode fouling may take place and provides insight into the identity of side-product pathways.
Considering the frequent use of netupitant in polytherapy, the elucidation of its oxidative metabolization pattern is of major importance. However, there is a lack of published research on the redox behavior of this novel neurokinin-1 receptor antagonist. Therefore, this study was performed to simulate the intensive hepatic biotransformation of netupitant using an electrochemically driven method. Most of the known enzyme-mediated reactions occurring in the liver (i.e.,
N
-dealkylation, hydroxylation, and
N
-oxidation) were successfully mimicked by the electrolytic cell using a boron-doped diamond working electrode. The products were separated by reversed-phase high-performance liquid chromatography and identified by high-resolution mass spectrometry. Aside from its ability to pinpoint formerly unknown metabolites that could be responsible for the known side effects of netupitant or connected with any new perspective concerning future therapeutic indications, this electrochemical process also represents a facile alternative for the synthesis of oxidation products for further in vitro and in vivo studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.