Ever since the discovery of insulin, peptides have been an integral component of therapeutic intervention for various diseases. Nowadays, with the advances in chemical synthesis and recombinant technology, peptide therapeutics plays an increasingly important role in improving human health. Today, more than 60 therapeutic peptides are used in clinics worldwide, with many more in the development pipeline.<br/> <br/>Implementation of quantitative analytical method for peptides in development is essential to a successful discovery and development pipeline.  In discovery and early development, LC-MS/MS is often selected as the analytical platform of choice because of its selectivity and versatility.  However, therapeutic peptides in biological matrices pose greater challenges than small molecules in LC-MS/MS method development because of the higher molecular weight, more complex structure, and more diverse chemical and physical properties. To meet the fast turnaround time in the early discovery space and satisfy the assay sensitivity required for peptides with pM potency, we often leverage SPE as the method of choice for peptides with a wide range of MW, hydrophobicity, and various post translational modifications.  In optimizing each assay, we strive for a balance between maximizing recovery and minimizing background interference.  Often this requires testing a combination of various sorbents and eluents.  Once the SPE condition for a certain class of peptides is established, the method is automated to increase the throughput and reduce assay variability.  In this talk, we will present examples of SPE method development for peptides in various structural classes, ranging from derivatives of insulin to modified incretins.  Details on optimization of pre-treatment of biological matrices and SPE sorbent selection will be discussed along with LC-MS/MS data exemplifying challenges in peptide analytical method development.

Solid phase extraction (SPE) in bioanalytical method development for therapeutic peptides

256th National Meeting (2018)

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