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).
Tassin
J P
JP
Université Libre de Bruxelles, Institut de Pharmacie, Laboratoire de Pharmacologie Cellulaire et Animale, Brussels, Belgium.
Dubois
J
J
Atassi
G
G
Hanocq
M
M
D000903:Antibiotics, Antineoplastic / Q000032:analysis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000032:analysis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000032:analysis / Q000494:pharmacology; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007624:KB Cells; D010880:Piperidines / Q000032:analysis / Q000494:pharmacology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D014227:Triazines / Q000032:analysis / Q000494:pharmacology; D014700:Verapamil / Q000032:analysis / Q000494:pharmacology; D014750:Vincristine / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D010880:Piperidines; D014227:Triazines; C077022:S 9788; D014750:Vincristine; D004317:Doxorubicin; D014700:Verapamil