Dimerization of Doxorubicin Causes Its Precipitation

Doxorubicin (DOX) is commonly used in chemotherapy and biomedical research because of its potent anticancer activity. Although DOX is water soluble, it precipitates when interacting with buffers, such as phosphate-buffered saline, or with drugs such as 5-fluorouracil (5-FU) and heparin. This study reports that DOX precipitates in neutral buffers and 5-FU solution because of the formation of covalently bonded DOX dimers. Additionally, this study proposes a structure for the DOX dimer and a mechanism for dimerization on the basis of mass spectrometry in combination with an experiment to establish the reaction model. The DOX dimer/precipitate formation might be an important phenomenon, considering the frequent use of DOX in chemotherapy and biomedical research.