Absorption and Metabolism Characteristics of Triptolide as Determined by a Sensitive and Reliable LC-MS/MS Method.

In this research, a sensitive and reliable LC-MS/MS method was developed and applied to determine the concentration of triptolide in rat plasma, microsomes, and cell incubation media. The absolute oral bioavailability of triptolide is 63.9% at a dose of 1 mg·kg-1. In vitro, the bidirectional transport of triptolide across Caco-2 cells was studied. A markedly higher transport of triptolide across Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. The result indicated that P-gp might be involved in the absorption of triptolide in intestinal. The metabolic stability was also investigated using human liver microsome incubation systems in vitro. In HLMs, incubations with an initial triptolide concentration of 1 μM resulted in an 82.4% loss of substrate over 60 min, and the t1/2 was 38 min, which indicated that triptolide was easily metabolized in human liver microsomes. In conclusion, the absolute oral bioavailability of triptolide in plasma, transport across Caco-2 cell monolayers, and metabolic stability in human liver microsomes were systematically investigated by using a sensitive and reliable LC-MS/MS method.