Pharmacokinetics and tissue distribution of tripchlorolide in rodents using liquid chromatography tandem mass...

Tripchlorolide is a promising therapeutic compound with potent pharmacological activity and an improved safety profile compared to triptolide. However, its pharmacokinetics and tissue distribution remain poorly characterized. In this study, we developed and validated a rapid and sensitive liquid chromatography-mass spectrometry method for the quantification of tripchlorolide in biological matrices, using triptolide as the internal standard. Quantification was performed in selective ion monitoring mode, following liquid-liquid extraction with ethyl acetate. Chromatographic separation was achieved on a 3.5 μm Agilent ZORBAX Eclipse Plus-C18 column under isocratic elution with a methanol-water mobile phase. Calibration curves were linear over the range of 0.16-200 ng/mL in rat plasma. The method was successfully applied to a pharmacokinetic study in rats and tissue distribution analysis in mice. Tripchlorolide exhibited an absolute bioavailability of 72.97 % after intraperitoneal administration and a half-life of approximately 45 min, with no significant sex-based differences in pharmacokinetic parameters. Tissue distribution following intravenous administration (400 μg/kg) in mice revealed the highest accumulation in the liver, followed by the kidney, spleen, testis, heart, intestine, and brain. These findings provide essential preclinical data for further development of tripchlorolide as a safe and effective therapeutic candidate.