Metabolite profiling and quantification of phytochemicals of Tianma-Gouteng granule in human and rat urine using ultra high performance liquid chromatography coupled with tandem mass spectrometry.

Tianma-Gouteng granule has been used for the treatment of hypertension, headache, and stroke in China. However, the metabolism of Tianma-Gouteng granule has not been clear. In the present study, an ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method has been developed for rapid identification of 35 prototypes and 43 metabolites in human and rat urine after single oral administration of Tianma-Gouteng granule. The results showed that glucuronidation and sulfation were the main metabolic pathways for flavonoids, alkaloids, iridoidic glycosides, anthraquinones, phenols, and stilbenes that were found in Tianma-Gouteng granule. Moreover, a validated ultra high performance liquid chromatography coupled with tandem mass spectrometry method was applied for the quantification of 14 compounds in rat urine after an oral administration of Tianma-Gouteng granule (2.5 g/kg). During 0-48 h after dosing, the cumulative excretion rates of nine prototype components were 53% for gastrodin, 0.07∼1.6% for geniposide, baicalin and baicalein, wogonoside, rhynchophylline and isorhynchophylline, leonurine, and emodin, indicating that urinary excretion is the major way for gastrodin to eliminate from the body. This study provides a comprehensive understanding of metabolism and excretive kinetics of Tianma-Gouteng granule in human and/or rat, and helpful information for screening of its active components in vivo and clinical application.