Despite numerous studies of platinum-protein binding in the last few decades, the roles of platinum-protein adducts in drug action, and in toxicity of these drugs are not known. Although cisplatin-protein adducts are widely believed to cause the drug's side effects, there are also claims that platinum-protein adducts are important for the drug's activity. Therefore, a better understanding of the molecular mechanism of platinum-protein interactions may have an impact on the optimization of strategies for platinum treatment. It is important to understand basic principles that govern formation and reactivity of platinum-protein adducts because these adducts may be important in defining the therapeutic profile of these drugs. In this quest, the first goal is to develop a reliable technique for these studies. To date, ultraviolet/visible (UV-Vis), fourier transform infrared (FT-IR), and nuclear magnetic resonance (NMR) studies of cisplatin-protein interactions have provided only low-resolution information on the mechanism of the binding or on the nature of the adducts. The researchers propose to investigate the role of platinum-protein adducts in the mechanisms of the drug action and their contributions towards the toxicity of these drug. The short-term objective is to investigate platinum interaction with serum proteins using both nanoelectrospray mass spectrometry (nanoESI-MS) and a combination of size exclusion high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC/ICP-MS). The long-term objective of this research is to develop biomarkers based on platinum-protein adducts for clinical monitoring.