Pharmacokinetics and tissue distribution study of two novel quinazoline PI3K/mTOR dual-inhibitors, potential anticancer agents.

S₁ and S₂, two structurally similar quinazoline derivatives, are novel anticancer drugs targeting the PI3K/AKT/mTOR signaling pathway channel. However, their pharmacokinetic and tissue distribution characteristics are unknown, which has hindered further development and in-depth studies. In this study, a simple, rapid and sensitive method using high performance liquid chromatography was established and validated to quantitatively study the pharmacokinetics and tissue distribution profiles of S₁ and S₂ in rats following intravenous injection. The results indicated that after intravenous injection, the elimination of S₁ and S₂ fit the two-compartment model and linear pharmacokinetics characteristics were observed. Furthermore, S₁ and S2 were widely distributed and found in high concentrations in liver and kidney tissues and a small proportion of S₁ and S₂ could cross the blood-brain barrier and be distributed in the brain. The current findings will contribute to interpretation and understanding the relationship between dosage and pharmacodynamic effects of S₁ and S₂.