Studies in drug albumin binding using HSA and RSA affinity methods

A HPLC gradient methodology using immobilized human serum albumin (HSA) and rat serum albumin (RSA) has been used as a tool to investigate the protein binding trends of novel discovery compounds. These methods have been set up to support a high throughput approach and have been shown to be complementary to one another. Significant binding differences have been observed with some compounds when both methods have been employed. Discovery chemists are now also able to rank order molecules using these quick “trend analysis” albumin binding screens by submitting a 20 µl sample from the 10 mM stock solution from the inhouse compound archive. Additionally, chemists have the opportunity to predict trends in albumin binding by use of an internal QSAR model based upon a diverse 1200 compound result set, which had been previously analyzed with the HSA methodology.