Metabolic Stability and Metabolic Profile of Schisandrol B in Rat and Human Liver Microsomes Employing HPLC‐MS/MS Analysis

RATIONALE: Schisandrol B (Sol B) is a major bioactive lignan compound extracted from the dried fruits of Schisandra chinensis (Turcz.) Baill. with comprehensive pharmacological activities. The study aims to investigate the metabolic stability and metabolic characteristics of Sol B in rat liver microsomes (RLMs) and human liver microsomes (HLMs) and further clarify the metabolic differences among different species. METHOD: The in vitro incubation systems included 5 μM Sol B and 0.5 mg/mL HLMs or RLMs in the presence of NADPH (5 mM) at 37°C in 200 μL phosphate-buffered saline. The residual amount of Sol B in the incubation system at different time points was determined to calculate the metabolic stability. The main metabolites of Sol B were identified and further elucidated the main metabolic pathways of Sol B. RESULTS: was calculated as 33.6 min and 75.21 min, respectively. A total of seven metabolites were detected in RLMs and HLMs systems. Metabolites M402-1 and M384-1 were detected only in the RLMs incubation system, while all other metabolites were monitored in both RLMs and HLMs incubation systems. Main metabolic pathways of Sol B in RLMs and HLMs mainly include dehydration, O-demethylation, and oxidative dehydrogenation. CONCLUSIONS: The metabolic behavior of Sol B in RLMs and HLMs exhibited certain species differences. Overall, Sol B was more stable in HLMs, with relatively simpler metabolic pathways.