Chemical and electrochemical oxidation of 7-hydroxychlorpromazine

Neptune, Marilyn; McCreery, Richard L.

doi:10.1021/jm00202a010

Cited by 21 publications

(12 citation statements)

References 8 publications

(11 reference statements)

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“…The lower oxidation potential of this metabolite is due to the presence of the ring hydroxyl group. A possible mechanism of electrochemical oxidation of hydroxylated derivatives could be explained by the formation of a quinone imine (8). Similar current-potential curves were observed with imipramine, desmethylimipramine, and their 2-hydroxy metabolites under similar experimental conditions (2).…”

Section: Resultssupporting

confidence: 66%

Determination of Mianserin and Metabolites in Plasma by Liquid Chromatography with Electrochemical Detection

Suckow¹,

Cooper²,

Quitkin³

et al. 1982

Journal of Pharmaceutical Sciences

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Section: Resultssupporting

confidence: 66%

Determination of Mianserin and Metabolites in Plasma by Liquid Chromatography with Electrochemical Detection

Suckow¹,

Cooper²,

Quitkin³

et al. 1982

Journal of Pharmaceutical Sciences

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“…This isotonic acetate buffer system was selected because it was reported to provide acceptable stability to CPZ and to have the least solute-buffer interactions. 27,29 CPZ undergoes its first oxidation at 0.65 V vs SCE and its second oxidation at 1.2 V vs SCE. Figure 2 shows the typical CV run between 0 and 1.2 V vs SCE at 50 mV/s with a graphite disk macroelectrode.…”

Section: Methodsmentioning

confidence: 99%

Short-Term Chronoamperometric Screening of Chlorpromazine-Package Interactions

Sarsfield

Maloy

1998

Journal of Pharmaceutical Sciences

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A new electroanalytical method has been developed to measure and predict solute sorption interactions with solid surfaces. By maximizing surface-to-volume ratios, this method significantly reduces the study time of drug-package interactions and allows prediction of possible long-term effects. Chronoamperometry experiments were run in 40 microL drops of solution containing drug placed on a solid substrate disk of about 7 mm diameter in a sample cell designed to accommodate a miniaturized three-electrode setup. Logarithmic current signatures obtained by computing Delta(ln i)/Delta(ln t) were used to define the experimental conditions necessary to avoid the kinetic complications of chlorpromazine oxidation in the interpretation of the results of the chronoamperometric analysis. Results of sorption studies of chlorpromazine to glass, polypropylene, high density polyethylene, poly(ethylene terephthalate), ethylene vinyl acetate, and poly(vinyl chloride) are presented. The small volume sorption experiments demonstrated that chlorpromazine interacts most quickly with PVC and HDPE and least with glass and polypropylene. Long term stability tests confirmed these predictions, thereby indicating that the small volume method makes drug-package interaction studies feasible in early development. The generation and analysis of Delta(ln i)/Delta(ln t) signature curves extends the usefulness of the electroanalytical method to other systems by accurately identifying the appropriate time domains for steady state or Cottrell behavior.

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“…• Peroxidase catalysed formation of the sulfur cation radical form of chlorpromazine. 103 • Ring hydroxylations by P450 processes at the 7 [104][105][106] and 8 105 positions. This leads to further oxidations forming 7,8-dioxochlorpromazine.…”

Section: Chlorpromazinementioning

confidence: 99%

Defining Molecular Initiating Events in the Adverse Outcome Pathway Framework for Risk Assessment

Allen

Goodman

Gutsell

et al. 2014

Chem. Res. Toxicol.

148

106

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Consumer and environmental safety decisions are based on exposure and hazard data, interpreted using risk assessment approaches. The adverse outcome pathway (AOP) conceptual framework has been presented as a logical sequence of events or processes within biological systems which can be used to understand adverse effects and refine current risk assessment practices in ecotoxicology. This framework can also be applied to human toxicology and is explored on the basis of investigating the molecular initiating events (MIEs) of compounds. The precise definition of the MIE has yet to reach general acceptance. In this work we present a unified MIE definition: an MIE is the initial interaction between a molecule and a biomolecule or biosystem that can be causally linked to an outcome via a pathway. Case studies are presented, and issues with current definitions are addressed. With the development of a unified MIE definition, the field can look toward defining, classifying, and characterizing more MIEs and using knowledge of the chemistry of these processes to aid AOP research and toxicity risk assessment. We also present the role of MIE research in the development of in vitro and in silico toxicology and suggest how, by using a combination of biological and chemical approaches, MIEs can be identified and characterized despite a lack of detailed reports, even for some of the most studied molecules in toxicology.

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Chemical and electrochemical oxidation of 7-hydroxychlorpromazine

Cited by 21 publications

References 8 publications

Determination of Mianserin and Metabolites in Plasma by Liquid Chromatography with Electrochemical Detection

Determination of Mianserin and Metabolites in Plasma by Liquid Chromatography with Electrochemical Detection

Short-Term Chronoamperometric Screening of Chlorpromazine-Package Interactions

Defining Molecular Initiating Events in the Adverse Outcome Pathway Framework for Risk Assessment

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