First Establishment of LC–MS/MS Method for Quantitative Analysis of Pharmacokinetics and Tissue Distribution of Trilobatin—Comparison of Three Administration Modes

Trilobatin is a novel dihydrochalcone natural food additive. It has multiple functions such as anti-inflammatory, antioxidant, and anticancer effects. This study first developed and validated a method based on liquid chromatography-tandem mass spectrometry for the quantitative determination of trilobatin in rat plasma and tissues. The method demonstrated high precision, high accuracy, good extraction recovery, and minimal matrix effects. Subsequently, this method was used to study the pharmacokinetics and tissue distribution of trilobatin after oral, intravenous, and intraperitoneal administration in rats. Pharmacokinetic analysis showed that trilobatin was rapidly absorbed after oral administration with a Tmax of 1 h, and Tmax was also approximately 1 h after intraperitoneal administration. Compared to intravenous injection, the relative bioavailability of oral administration and intraperitoneal injection is only 0.004% and 0.3%, respectively. Tissue distribution results from the three administration routes indicated that trilobatin exhibits widespread tissue distribution. These findings provide a theoretical basis for further research on trilobatin. This study provides detailed insights into the pharmacokinetic and tissue distribution characteristics of trilobatin in rats for the first time, laying the foundation for further research on trilobatin as a potential new drug candidate.