Contributions
Abstract: PB2487
Type: Publication Only
Background
Treosulfan is an alkylating agent that is used for the treatment of ovarian cancer and for conditioning prior to stem cell transplantation. It is a prodrug that is activated non‑enzymatically to two active metabolites.
Aims
To optimize a protocol for both in vivo samples handling and in vitro drug preparation.
Methods
Treosulfan stability was tested in biological fluids at different conditions as well as for plasma binding and drug cytotoxicity on cell lines.
Results
Plasma samples can be safely frozen for short period up to 8h, however; for longer periods, samples should be acidified. Urine samples and cell culture media can be safely frozen regardless the pH. For in vitro investigations, incubation of treosulfan at 37oC for 24h activated 100% of the drug.
Treosulfan binding to plasma proteins was 10% and it was safe to separate the plasma from whole blood without affecting treosulfan concentrations. Whole blood acidification should be avoided for the risk of hemolysis.
Finally, the HL-60 cell line was more sensitive to treosulfan compared to K562 cell line and the drug cytotoxicity increased following pre-incubation for 24h at 37oC.
Conclusion
The stability profiling of treosulfan provided a valuable reference for proper handling of biological samples for both in vivo and in vitro studies. These results can be utilized as a corner stone for further investigations that will enable better understanding for the drug kinetics and dynamics. Such studies are required in order to personalize treosulfan treatment, reduce its toxicity and improve the clinical outcome.
Session topic: 22. Stem cell transplantation - Experimental
Keyword(s): toxicity, Treosulfan
Abstract: PB2487
Type: Publication Only
Background
Treosulfan is an alkylating agent that is used for the treatment of ovarian cancer and for conditioning prior to stem cell transplantation. It is a prodrug that is activated non‑enzymatically to two active metabolites.
Aims
To optimize a protocol for both in vivo samples handling and in vitro drug preparation.
Methods
Treosulfan stability was tested in biological fluids at different conditions as well as for plasma binding and drug cytotoxicity on cell lines.
Results
Plasma samples can be safely frozen for short period up to 8h, however; for longer periods, samples should be acidified. Urine samples and cell culture media can be safely frozen regardless the pH. For in vitro investigations, incubation of treosulfan at 37oC for 24h activated 100% of the drug.
Treosulfan binding to plasma proteins was 10% and it was safe to separate the plasma from whole blood without affecting treosulfan concentrations. Whole blood acidification should be avoided for the risk of hemolysis.
Finally, the HL-60 cell line was more sensitive to treosulfan compared to K562 cell line and the drug cytotoxicity increased following pre-incubation for 24h at 37oC.
Conclusion
The stability profiling of treosulfan provided a valuable reference for proper handling of biological samples for both in vivo and in vitro studies. These results can be utilized as a corner stone for further investigations that will enable better understanding for the drug kinetics and dynamics. Such studies are required in order to personalize treosulfan treatment, reduce its toxicity and improve the clinical outcome.
Session topic: 22. Stem cell transplantation - Experimental
Keyword(s): toxicity, Treosulfan