Evaluation of Acute Pharmacokinetics and Liver Metabolic Response of L -Se-Methylselenocysteine in Mice Using UPLC-QqQ-MS/MS and Untargeted Metabolomics

Abstract L-Se-methylselenocysteine (L-SeMC) is a natural organic selenium compound with potential nutritional applications, but its acute disposition and metabolic responses remain incompletely characterized. Here, UPLC-QqQ-MS/MS was used to characterize L-SeMC pharmacokinetics and tissue distribution in H22 tumor-bearing mice, while untargeted metabolomics was applied to assess hepatic responses after acute administration. L-SeMC was rapidly absorbed, reaching peak plasma and tumor concentrations within 5 and 30 min, respectively. The liver and tumor showed relatively high exposure, whereas parent L-SeMC declined to near-baseline levels within 2880 min. In contrast, hepatic metabolic alterations were most pronounced at 1440 min and were mainly associated with sulfur amino acid metabolism, accompanied by increased glutathione and taurine. These findings provide a clearer characterization of the acute pharmacokinetic behavior and hepatic metabolic responses of L-SeMC and establish a pharmacokinetic basis for further investigation of its biological effects and nutritional potential.