Evaluation of the effects of four types of tea on the activity of cytochrome P450 enzymes with a probe cocktail and HPLC-MS/MS

BACKGROUND: Tea, the world’s second most popular drink, is an essential part of some people’s lives. Thus, this study aimed to explore potential tea-drug interactions with a view to promoting the rational administration of drugs. METHODS: A specific and sensitive approach involving high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and a probe cocktail was established and validated to evaluate the inhibitory effects of four teas on five cytochrome P450 (CYP450) enzymes in rats. Metoprolol tartrate (MT), omeprazole (OMP), phenacetin (PNT), tolbutamide (TOL), and testosterone (T) were selected as the probe drugs for CYP2D6, CYP2C19, CYP1A2, CYP2C6, and CYP3A1/2, respectively, and were simultaneously quantified in the multiple reaction monitoring (MRM) mode with positive electrospray ionization (ESI+) in a single 12-min run. RESULTS: The extraction recoveries, matrix effect values, as well as intra/interday accuracy and precision met the determination standards. CYP1A2 and CYP2C6 were strongly inhibited by green tea, and CYP2C6 was also strongly inhibited by Pu’er tea. Ti Kuan Yin tea had a weak inhibitory effect, and black tea had only a slight inhibitory effect, on CYP1A2. Furthermore, the four types of tea did not have significantly altered the activity of CYP2D6, CYP2C19, and CYP3A1/2 in vitro. CONCLUSIONS: The method used in the present study was successfully applied to assess the inhibitory effects of aqueous extracts of four types of tea on CYP450 isoforms in vitro. The results suggest that different types of tea have different effects on drug metabolism.