The antitumor activity and pharmacokinetics research of PPD‐Arg (Tos) using ultra‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry

Abstract In this study, a new compound PPD‐Arg (Tos) (PAT), an arginine derivative of 20(s)‐PPD, was synthesized via Fmoc‐Arg (Tos)‐OH and 20(s)‐PPD. The pharmacokinetic properties in rats, in vitro cytotoxicity, and cell apoptosis rates of protopanaxadiol (PPD) and PAT were determined. A sensitive bioanalytical method for pharmacokinetics using ultra‐performance liquid chromatography coupled with time‐of‐flight mass spectrometry was developed and validated. The result showed that the T max and t 1/2 of PAT were significantly enhanced, indicating a long‐lasting effect in vivo . Compared to the PPD group, the PAT group showed higher bioavailability. PAT also exhibited higher antitumor efficacy than PPD against three cancer cells, especially the strongest inhibitory activity against Huh‐7, even more potent than the positive control of paclitaxel. Therefore, the apoptosis assay based on annexin V/propidium iodide–combined staining against Huh‐7 further demonstrated that PAT could induce apoptosis of Huh‐7 cells. Better pharmacokinetic properties and antitumor efficacy of the arginine derivative of 20(s)‐PPD were important. These findings could provide references for further clinical research on amino acid derivatives of PPD as antitumor agents.