OBJECTIVE: To study the inhibition effect of spinosin on 7 subtypes (CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP1A1, CYP2C19 and CYP3A4) of cytochrome P450 (CYP450) enzymes from human liver microsomes in vitro. METHODS: Taking 200.00, 100.00, 50.00, 25.00, 12.50, 6.25, 3.13, 1.56, 0.78, 0.39 μmol/L spinosin and human liver microsomes for incubation, using daktarin, bupropion, amodiaquine hydrochloride, diclofenac sodium, mephenytoin, dextromethorphan hydrobromide and midazolam as the specific probe drugs for above-mentioned 7 subtypes of CYP450 enzymes. UPLC-Q-TOF-MS was conducted to detect generation amount of 7 probe drug metabolites, and the half inhibitory concentration (IC50) of spinosin on 7 subtypes of CYP450 enzymes from human liver microsomes was calculated. RESULTS: IC50 of spinosin on 7 subtypes of CYP450 enzymes from human liver microsomes were 1 714, 1 158, 226.1, 2 288, 80.59, 101.1, 1 119 μmol/L, respectively, which were higher than 50 μmol/L. CONCLUSIONS: Spinosin has no inhibition effect on above-mentioned 7 subtypes of CYP450 enzymes from human liver microsomes, with very low probability of inducing metabolic drug interactions.