Determination of the effect of berberine on epirubicin concentration in MCF-7 cells by LC-MS/MS: The mechanism of synergism explained by intracellular pharmacokinetics

This study investigated the inhibitory effect of epirubicin combined with berberine on MCF-7 cell proliferation and explored intracellular pharmacokinetics. A CCK-8 assay was used to detect the inhibitory effect of epirubicin alone and in combination with berberine on MCF-7 cell proliferation in vitro. A rapid and sensitive LC-MS/MS method was developed and validated to detect epirubicin in MCF-7 cells. After incubation with epirubicin and berberine at different time points, MCF-7 cells were lysed and precipitated by acetonitrile to extract the analyte. Chromatographic separation was performed on a C18 column. Daunorubicin was selected as the internal standard. The analytical method was applied to determine the epirubicin concentration in MCF-7 cells. Berberine was found to enhance the inhibitory effect of epirubicin (1 μg/mL and 2 μg/mL) on the proliferation of MCF-7 cells (P < 0.05). LC-MS/MS analysis revealed that berberine significantly increased epirubicin concentration in MCF-7 cells at 8, 12, and 24 h (P < 0.05). The results suggest that berberine may enhance the inhibitory effect of epirubicin on cell proliferation by increasing the concentration of epirubicin in MCF-7 cells. The assay provides a basis for research on the intracellular pharmacokinetics of epirubicin and develops analytical methods for other cell-targeted drugs.