Development of a method for quantitative determination and preliminary pharmacokinetics study of a new anticancer agent

For the treatment of cancer, inhibitors of the reparation systems are needed. One of the specific targets is the enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1). Inhibition of this enzyme can increase the sensitivity of tumor cells to drugs used to treat cancer. Earlier, the substance KS-389 was obtained, which in in vitro experiments showed a synergistic effect against glioblastoma cells when was administrated together with temozolomide. In this work we developed a HPLC-MS/MS method for the quantittion of the agent KS-389 in mice whole blood. A calibration curve was obtained in a concentration range of 2-2000 ng/ml. Using the developed method, a preliminary pharmacokinetics study of the substance was carried out.

When administered intraperitoneally at a dose of 5 mg/kg, a dosage form based on tween-80 provided better bioavailability compared to oral administration. The maximum concentration of KS-389 of about 450 ng/ml was observed 1.5-2 hours after administration. The full clearance of the agent was 6 hours after the administration showing normal pattern of the pharmacokinetics.