Eupatorin is the major bioactive component of Java tea (Orthosiphon stamineus), exhibiting strong anticancer and anti-inflammatory activities. However, no research on the metabolism of eupatorin has been reported to date. In the present study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) combined with an efficient online data acquisition and a multiple data processing method were developed for metabolite identification in vivo (rat plasma, bile, urine and feces) and in vitro (rat liver microsomes and intestinal flora). A total of 51 metabolites in vivo, 60 metabolites in vitro were structurally characterized. The loss of CH₂, CH₂O, O, CO, oxidation, methylation, glucuronidation, sulfate conjugation, N-acetylation, hydrogenation, ketone formation, glycine conjugation, glutamine conjugation and glucose conjugation were the main metabolic pathways of eupatorin. This was the first identification of metabolites of eupatorin in vivo and in vitro and it will provide reference and valuable evidence for further development of new pharmaceuticals and pharmacological mechanisms.

Introduction: Effective perioperative analgesia in liver cancer patients presents an ongoing clinical challenge. This study investigates oxycodone’s pharmacokinetics in perioperative liver cancer patients with normal liver function to support individualized analgesia. Methods: This study developed and validated a reliable high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous quantification of oxycodone and its metabolite noroxycodone in human plasma. The method was successfully applied to characterize the pharmacokinetics in nine surgical liver cancer patients following intravenous oxycodone administration, using non-compartmental analysis (NCA). Results: The developed method showed satisfactory linearity and met validation criteria. In perioperative liver cancer patients, oxycodone exhibited reduced clearance, prolonged half-life, increased volume of distribution, and elevated exposure compared with healthy volunteers. Its metabolite noroxycodone displayed a biphasic profile with consistently higher concentrations in males. Significant sex-related differences were also observed for oxycodone’s area under the plasma concentration-time curve (AUC) and mean residence time (MRT). Discussion: This study reveals that compared with healthy volunteers, perioperative liver cancer patients with normal liver function exhibit significantly altered oxycodone pharmacokinetics, including reduced clearance, prolonged half-life, increased exposure and volume of distribution, with notable sex differences. These findings support the need for dose reduction, extended monitoring, and individualized analgesic strategies.