Metabolites, studied electrochemically

Electrochemical oxidation reactions have been fonnd to mimic cytochrome P450 catalysed oxidation reaction to some extent, and can therefore be used as a tool in performing preliminary drug metabolism studies. Combined electrochemistry-mass spectrometry was explored for drug metabolite studies [77-78],... 

Liquid chromatographic electrochemical detection has been widely used for metabolite studies in complex matrices and has general applicability in many helds, for example, the pharmaceutical industry, forensic science, medicine, the explosives industry, and agriculture. 

It is, however, quite clear from studies of the electrochemical and other oxidations of chlorpromazine and some of its hydroxylated metabolites that electrochemical techniques provide powerful tools to generate and detect transient intermediates and products and provide valuable insights into reaction mechanisms. It has yet to be demonstrated whether the electrode and related chemical mechanisms will prove to be the same as or similar to in vivo processes. Nevertheless, the present evidence supports the conclusion that there is a very likely correlation between the the biological and electrochemical processes. 

Imperato, A., and Di Chiara, G. Transtriatal dialysis coupled to reverse-phase high performance liquid chromatography with electrochemical detection A new method for the study of the in vivo release of endogenous dopamine and metabolites. J Neurosci A.966-911, 1984. 

In the case of the methylated xanthines, particularly theophylline, theobromine and caffeine, the preponderance of data on the metabolism of these compounds in man suggests that a methylated uric acid is the principal product. However, the data presented earlier proposes at best a 77 per cent accounting of the methylated xanthine administered. The question can be raised as to whether the final products observed upon electrochemical oxidation of these compounds aids these studies. Very recently studies of metabolism of caffeine have revealed that 3,6,8-trimethylallantoin is a metabolite of caffeine 48>. This methylated allantoin is, of course, a major product observed electrochemically. The mechanism developed for the electrochemical oxidation seems to nicely rationalize the observed products and electrochemical behavior. The mechanism of biological oxidation could well be very similar, although insufficient work has yet been performed to come to any definite conclusions. There is however, one major difference between the electrochemical and biological reactions which is concerned with the fact that in the former situation no demethylation occurs whereas in the latter systems considerable demethylation appears to take place. 

The initial electrochemical and biological oxidation with xanthine oxidase are essentially identical. However, electrochemically 2,8-dioxyadenine the final product in the presence of xanthine oxidase is much more readily oxidizable than adenine 59) so that considerable further oxidation occurs. To the authors knowledge, 2,8-dioxyadenine is not a major metabolite of adenine in man or other higher organisms. Accordingly, it is likely that other enzymes accomplish further degradation of 2,8-dioxyadenine. The relationship between the products so formed and the mechanism of the reaction to the related electrochemical processes has yet to be studied. 

Madsen, K.G. et al. (2007) Development and evaluation of an electrochemical method for studying reactive phase-I metabolites correlation to in vitro drug metabolism. Chemical Research in Toxicology, 20 (5), 821-831. 

The electrochemical study of the in situ interaction of quercetin, adriamycin, DETA/NO and their metabolites with double-stranded DNA (dsDNA) immobilized on a glassy carbon electrode (GCE) surface. 

To study the interaction between dsDNA and quercetin metabolites, a multi-layer newly prepared biosensor is immersed for 10 min in a solution of 100 pM quercetin. After incubation, the biosensor is washed in water and transferred to another electrochemical cell that contains only pure supporting electrolyte. A... 

Baranowska, I., Koper, M. The preliminary studies of electrochemical behavior of paracetamol and its metabolites on glassy carbon electrode by voltammetric methods. Electroanalysis 21, 1194-1199 (2009)... 

Khalil, M. Gonnet, C. Simultaneous determination of aspirin, its major metabolites, acetaminophen and phen-acetin by liquid chromatography. Comparative study of electrochemical and UV detection. Anal. Chem. S5Tnp. Ser. 1983, 14, 85-95. 

DHT raises the possibility that one or more of these other putative aberrant oxidative metabolites might play roles in the neurodegenerative effects evoked by methamphetamine. The influence of CySH on the HO-mediated oxidation of 5-HT remains to be studied. However, recent studies into the electrochemically driven oxidation of 5-HT in the presence of CySH suggest that many additional products are likely to be formed (Wrona et al. 1994). 

Radiochemical and immunochemical techniques of detection may offer improvements in sensitivity over conventional detection methods for proteins. These techniques have been applied in the HPLC of biogenic amines (M7) and of drugs and drug metabolites (T9), but not as yet in the HPLC of proteins. Similarly, there has been little study of the electrochemical detection of proteins. 

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