Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays

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Abstract
The methods used to test drug stability are discussed in the light of two recent publications using biological assays. It is concluded that, as far as possible, stabilityindicating assays should be used so that possible false results do not lead to erroneous conclusions. Many of the results of the stability studies with adriamycin were found to be at variance with each other, with a 20-fold difference in stability being reported in one case by different groups from virtually identical experiments. Definitive statements about adriamycin stability are therefore impossible, but it is clear that it is sensitive to light, adsorbs to membrane filters and containers (except polypropylene and siliconised glass), chelates metal ions and probably degrades rapidly in medium. Adriamycin's analogues may well have the same spectrum of sensitivity. Bleomycin, actinomycin D and neocarzinostatin were found to be stable for ≥2 weeks at room temperature. All the other antitumour antibiotics investigated (except rubidazone) are stable for ≥24 h at room temperature and longer at 5°C. Almost all of them are sensitive to light and are most stable in neutral or slightly acid media, and many of them adsorb to membrane filters. They can probably all be stored frozen in solution.