Conclusion
Treosulfan does not undergo either spontaneous or enzymatic conjugation with GSH at a noticeable rate. The result indicates that the clearance of treosulfan is independent of glutathione S-transferase activity, GSH stores, and co-administration of drugs utilizing the GSH metabolic pathway.
Methods
Treosulfan (200 μM) was incubated at pH 7.2 and 37 °C with 5 mM GSH in the presence or absence of human liver cytosol, the main store of glutathione S-transferase in the body. Concentrations of treosulfan were determined using liquid chromatography-tandem mass spectrometry and then subjected to kinetic analysis.
Results
The decay of treosulfan in the solution followed a one-exponential model in the presence of either GSH or liver cytosol and GSH. The first-order reaction rate constants (0.25 h-1) did not differ statistically from those found for treosulfan conversion in pH 7.2 buffer only.