A rapid bioassay to determine stabilities of anticancer agents under conditions of the clonogenic assay

We developed a rapid bioassay to determine in vitro drug stabilities in the clonogenic assay. The in vitro half-lives of 11 standard antitumor agents, actinomycin D, Adriamycin, bleomycin, cis-Platinum, dacarbazine, 5-fluorouracil, melphalan, mitomycin C, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), vinblastine, and vincristine, and four investigational drugs, Aziridinylbenzoquinone (AZQ) (NSC 182986), diamminecyclobutane-dicarboxylatoplatinum (CBDCA) (NSC 241240), Dihydroxyanthracenedione dihydrochloride (DHAD) (NSC 301739), and 1-(2-chloroethyl)-3-(2,6-dioso-3-piperidyl-1-nitrosourea) (PCNU) (NSC 95466), were determined under conditions of the clonogenic assay as well as under storage conditions at -40 degrees and -196 degrees C. BCNU and AZQ at -40 degrees C had t1/2 of 4.7 d 2.5 d, respectively. All other drugs were stable at -40 degrees and -196 degrees C with t1/2 greater than 6 wk. Under assay conditions at 37 degrees C, actinomycin D, bleomycin, dacarbazine, 5-fluorouracil, mitomycin C, vinblastine, vincristine, and DHAD were stable, with t1/2 greater than 14 d. CBDCA, AZQ, Adriamycin, cis-Platinum, melphalan, BCNU, and PCNU had t1/2 of 94,72,29,18.5,1.8,1, and 0.5 h, respectively.