Pharmacokinetic study of ZS-1, a targeted peptide to NCI-H1299, in rats following intravenous administration

摘要

To investigate the pharmacokinetics of ZS-1 following intravenous injection in rats, ZS-1 was administered at doses of 20, 30 and 45 mg kg~(-1), respectively. Blood samples were collected at 0.5, 3, 8, 12, 15, 20, 30, 40 and 45 min. ZS-1 in rat plasma was measured by LC. The limit of detection (LOD) was 0.02 μg mL~(-1). The relative standard deviation (RSD) of intra- and inter-day precisions were <10%, and the accuracy of intra- and inter-day were >94%. The mean extraction recovery of ZS-1 was 86.1%. After intravenous injection at doses of 20, 30 and 45 mg kg~(-1), the concentration-time curves of ZS-1 fitted well to one compartment model. Area under the concentration-time curves (AUC) increased with dose. Clearance rates (CL) and elimination half-lives (T _(1/2)) had no significant difference between different dose groups (P > 0.05). ZS-1 was stable in plasma after at 25 °C for 2, 4, 6 h, after three freeze-thaw cycles, after -20 °C for a month, and after -80 °C for 3 months. The accuracy of ZS-1 was between 96.8 and 106.9%. The results indicated there was no significant degradation. These data indicated that the method for analysis of ZS-1 was reliable and the pharmacokinetic data could guide dosing regimens to be tested in future clinical pharmacokinetic study.