Physicochemical characteristics of ferric adriamycin complexes.

Ferric ions and adriamycin in solution interact to form complexes that can yield colloidal and flocculant mixtures. At high concentrations (Fe3+ greater than or equal to 10(-4) M, adriamycin greater than or equal to 10(-5) M) an absorption appears at 600 nm, indicating colloid formation, which is directly responsive to concentrations of the reactants. Evidence from dilution experiments by spectral analysis, ultracentrifugation, titration, and filtration indicate that phase transition that is sensitive to pH and time occurs with iron-adriamycin complexes to yield flocculated drug. We conclude that patients and animals treated with the iron-adriamycin preparations known as 'quelamycin' received flocculated iron-adriamycin, which accounts for the toxic and pharmacologic effects reported. It may be useful to utilize colloidal preparations of reactive or irritating drugs to avert acute toxic effects and to produce slower release of active drug.