Electrochemical oxidation by square-wave potential pulses in the imitation of phenacetin to acetaminophen biotransformation

Analyst. 2011 Dec 7;136(23):5064-7. doi: 10.1039/c1an15643h. Epub 2011 Oct 7.

Abstract

Electrochemistry in combination with mass spectrometry is emerging as a versatile analytical technique in the imitation of oxidative drug metabolism during the early stages of drug discovery and development. Here, we present electrochemical O-dealkylation of phenacetin to acetaminophen by square-wave potential pulses consisting of consecutive sub-second oxidation and reduction steps. This O-dealkylation could not be achieved by oxidation at constant potential or longer potential pulses because of the fast hydrolysis of the reactive intermediates. Electrochemical conversion by square-wave potential pulses can thus widen the scope of electrochemical synthesis of metabolites and imitation of in vivo drug metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / chemistry*
  • Acetaminophen / metabolism
  • Biotransformation
  • Dealkylation
  • Drug Discovery / methods
  • Electrochemical Techniques / methods*
  • Mass Spectrometry / methods
  • Oxidation-Reduction
  • Pharmaceutical Preparations / chemistry
  • Phenacetin / chemistry*
  • Phenacetin / metabolism

Substances

  • Pharmaceutical Preparations
  • Acetaminophen
  • Phenacetin