Characterization and Control of Impurities in the Synthesis of an Amino Acid Drug Candidate

Abstract

The identification of process related impurities and elucidation of the mechanism for their formation can provide invaluable input for the optimization of a pharmaceutical synthetic process. The final two steps for the synthesis of an amino acid drug candidate involve the formation of an aminonitrile followed by its hydrolysis to the amino acid. The degradation impurities were generated in both steps. The degradation products were characterized and the mechanisms for their formation were proposed. This information was then fed back to the process chemists to minimize impurity formation.

Keywords:

• Drug candidate
• Identification of impurities
• Degradation mechanism

Acknowledgments

The authors would like to acknowledge Frederick W Hartner in Process Research for providing the test compounds, Lushi Tan from Process Research, and Peter Yehl, Naijun Wu, Tom Novak, and Lili Zhou in Analytical Research for their technical advice and valuable discussion.