Electrochemistry meets enzymes: instrumental on-line simulation of oxidative and conjugative metabolism reactions of toremifene.
The metabolism of the selective estrogen receptor modulator toremifene was simulated in an on-line electrochemistry/enzyme reactor/liquid chromatography/mass spectrometry system. To simulate the oxidative phase I metabolism, toremifene was oxidized in an electrochemical (EC) flow-through cell at 1,500 mV vs. Pd/H2 to its phase I metabolites, some of which are reactive quinoid species. In the presence of glutathione-S-transferase (GST), these quinoid compounds react with glutathione, which is also the common detoxification mechanism in the body. While reacting with glutathione, the chlorine atom is eliminated from the toremifene moiety. Due to higher conversion rates, GST supplied in continuous flow proved to be more efficient than using immobilized GST on magnetic microparticles. In the absence of GST, not all GSH adducts are formed, proving the necessity of a phase II enzyme to simulate the complete metabolic pathway of xenobiotics in an on-line EC/LC/MS system.
Lohmann
Wiebke
W
Westfälische Wilhelms-Universität Münster, Institute of Inorganic and Analytical Chemistry, Corrensstr. 30, 48149 Münster, Germany.
Karst
Uwe
U
D055664:Electrochemical Techniques / Q000295:instrumentation* / Q000379:methods; D005982:Glutathione Transferase / Q000378:metabolism*; D013058:Mass Spectrometry; D015394:Molecular Structure; D009862:Online Systems / Q000295:instrumentation*; D010084:Oxidation-Reduction; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry; D017312:Toremifene / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*
D020845:Selective Estrogen Receptor Modulators; D017312:Toremifene; D005982:Glutathione Transferase