Peptide Analytical Methods In Drug Discovery And Development
Hanspeter Michel
Senior Principal Scientist, Hoffmann-La Roche Inc.
The complexity of analytical characterization of pharmaceutically active peptides is inadvertently linked to the respective phase of the project from early discovery to development. In parallel, the analytical complexity is also strongly dependent on the chemical structure of the peptide drug substance and on its form as a formulated drug product. Analytical tools and methods for the characterization of unmodified peptide drug substances are at a rather mature level. Among the basic tools and methods are mass spectrometry, amino acid analysis as well as N-terminal amino acid sequencing for the determination of the primary sequence structure. On the other hand, the characterization of modified peptides is more demanding.
Our experience with a PEG-modified Y2R agonist peptide is presented as an example to demonstrate the role and the impact of analytical results for the project progression. While the analytical characterization of peptide identity, purity, stability and content was relatively straight forward at the level of the unmodified peptide, it was very important for the downstream characterization of the PEG-modified peptide drug substance. Impurity and degradation product characterization was crucial, not only as a feedback tool for peptide synthesis and modification chemistry, but also for control of purity of the polymer modified drug substance. Examples are presented, to define purity, identity, stability and content at an early development level. The potential impact of peptide analytical tools for the characterization of peptide delivery systems is also discussed.
Ph.D. in Biochemistry at University of Berne, Switzerland
Post-Doctoral Fellow in Brookhaven National Laboratory and at the University of Virginia in Charlottesville
1993: Roche (Nutley) Manager of a laboratory for the mass spectroscopic characterization of peptides and proteins (Biochemistry Department)
Currently: Roche (Nutley) Manager of a protein and peptide sequencing core facility and mass spectrometry laboratory (Formulation Research Department)