Simultaneous determination of cytotoxic (adriamycin, vincristine) and modulator of resistance (verapamil, S 9788) drugs in human cells by high-performance liquid chromatography and ultraviolet detection

Multidrug resistance (MDR), which was described for structurally and mechanistically unrelated anticancer agents, was modulated in vitro by a series of compounds which were of different chemical origin. In this situation, the selection of a correct assay dosage to study the MDR modulation mechanism was a problem. We developed a high-performance liquid chomatography (HPLC) method which enabled the simultaneous determination of three major cytotoxins (adriamycin, daunorubicin, vincristine) and two well-known modulators (S 9788, verapamil). This assay was fully validated and was used to follow, for the first time, the uptake and accumulation behaviour of adriamycin and S 9788 co-incubated with resistant and sensitive cell lines (KB-3-1; KB-A1).