Isolation and identification of five impurities of ALB 109564(a) drug substance.

Four low-level impurities were detected during the development and scale up of the synthesis of ALB 109564(a). These impurities were isolated and characterized in order to determine how they originated in the drug substance. The information allowed the elimination of one impurity and a significant reduction in the relative abundance of the other three. A fifth impurity was detected in an accelerated stability study sample of the drug substance. The degradant was found to be the free acid resulting from the hydrolysis of the methyl ester within the indoline moiety of ALB 109564(a). The characterization of this impurity allowed for changes in the handling of the drug substance which minimized the formation of the impurity.