Simulation of the detoxification of paracetamol using on-line electrochemistry/liquid chromatography/mass spectrometry.
On-line electrochemistry/liquid chromatography/mass spectrometry was used to simulate the detoxification mechanism of paracetamol in the body. In an electrochemical flow-through cell, paracetamol was oxidized at a porous glassy carbon working electrode at a potential of 600 mV vs. Pd/H2 with formation of a quinoneimine intermediate. The quinoneimine further reacted with glutathione and/or N-acetylcysteine to form isomeric adducts via the thiol function. The adducts were characterized on-line by liquid chromatography/mass spectrometry. These reactions are similar to those occurring between paracetamol and glutathione under catalysis by cytochrome P450 enzymes in the body.
Lohmann
Wiebke
W
Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 30, 48149, Münster, Germany.
Karst
Uwe
U
D000082:Acetaminophen / Q000032:analysis* / Q000737:chemistry / Q000633:toxicity*; D000111:Acetylcysteine / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004563:Electrochemistry / Q000379:methods*; D005978:Glutathione / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D009862:Online Systems
D000082:Acetaminophen; D005978:Glutathione; D000111:Acetylcysteine