Abstract: Objective: To determine the equilibrium solubility and oil-water partition coefficient of methyl-p-benzoquinone, and
analyze the cytotoxic activity against different tumor cells. Methods: The equilibrium solubility and oil-water partition coefficient of
methyl-p-benzoquinone in different pH solutions were determined by shake flask-HPLC method. Chromatographic conditions: Ecosil-
C18 chromatographic column（ 4.6 mm×250 mm, 5 μm）, the mobile phase was acetonitrile-0.1% formic acid aqueous solution（ 70 :30）,
the flow rate was 1.0 mL/min, the detection wavelength was 250 nm, the column temperature was 30 ℃, and the injection amount was
10 μL. SwissADME and pkCSM were used to predict the drug likeness. The cytotoxic activity of methyl-p-benzoquinone
against HT29, CT26, Caco-2, Hela and HepG2 cells was analyzed by MTT method. Results: The equilibrium solubility of methyl-pbenquinone
in solutions with pH of 1.2, 2.0, 5.0, 6.7, 7.0 and 7.4 for 12 h was 7.65, 8.05, 9.31, 8.43, 9.33 and 7.93 mg/mL,
respectively, and the oil-water partition coefficients were 0.78, 0.80, 0.83, 0.82, 0.77, 0.82, respectively. The solubility and oil-water
partition coefficient predicted by SwissADME were consistent with the experimental results. At the same time, the prediction results
showed that methyl-p-benzoquinone had better drug likeness and weaker blood-brain barrier permeability. The IC50 of methyl-pbenzoquinone
against 5 cell lines were 7.98, 3.21, 8.96, 7.96, 6.31 μmol/L, respectively. Conclusion: HPLC method is simple and
feasible. Moreover, the solubility of methyl-p-benzoquinone can be properly enhanced under the condition of pH 5.0~7.0 solution. At
the same time, the ADME/T online prediction software for drugs has certain reliability. Methyl p-benzoquinone has significant
inhibitory effect on multiple cell lines such as HT29 and CT26.

Key words: methyl-p-benzoquinone, oil-water partition coefficient, drug likeness, equilibrium solubility, cytotoxicity