Analytical Technologies for Therapeutic Peptides

Therapeutic peptides are an emerging class of active pharmaceutical ingredients that, together with other classes of bioproducts, have been attracting considerable attention due to their unique advantages. Their structure is based on well-defined amino acid sequences that may or may not contain structural modifications, resulting in molecules that generally range from 500 to 5000 Da. Currently, many examples can be used as medicines related to hormones, growth factors, neurotransmitters, among others.

The first peptide to be studied in this field was insulin, a 51-amino-acid chain that was originally isolated in 1921 by Frederick Banting and Charles Best and went on to become the first peptide to be commercially available (1923). Today, there is an extensive list of commercially available peptides on the market, including the well-known GLP-1 analogues such as liraglutide, semaglutide, and tirzepatide.

While peptides represent enormous potential for the treatment of a wide range of diseases, it can be said that there are critical issues intrinsic to their structure: their stability and the risk of impurity generation. The basic structure of a peptide makes it highly susceptible to chemical or biochemical reactions, such as, for example, hydrolysis of the main chain. To increase stability, many therapeutic molecules incorporate structural modifications, such as non-natural amino acids, stereochemical alterations, or the introduction of chemical groups that modify their properties. Regardless, there are still many potential degradation pathways that can lead to the formation of degradation products with longer and shorter chains, deamidation products, oxidation products, and more. On the other hand, each amino acid coupling to the main chain can generate structural variants related to incomplete couplings, deletion sequences, formation of epimers, among others.

YMC’s differentiator lies in the fact that the company offers solutions across the entire liquid chromatography workflow, from the analytical to the purification stage, creating a unique opportunity to use analytical columns together with chromatographic resins to obtain products with high purity and greater safety for consumption.

In the analytical segment, the main product line that can be discussed is the YMC-Triart line. Triart (U)HPLC columns and resins are manufactured using state-of-the-art hybrid silica technology, making them an ideal option for applications requiring extreme pH or temperature conditions. In the example below, results obtained with Triart C18 for liraglutide at three different working pH ranges can be found, with the aim of identifying the best chromatographic profile.

References: https://www.ymcamerica.com/wp-content/uploads/2022/01/AppNotePurificationPeptidesFIN-002-2.pdf 

At the analytical level, the selectivity of an analyte can be drastically altered by the mobile-phase composition, particularly its pH. There are situations where even more alkaline pH values than 8.5 are required. This is a critical point where many columns fail. In the example below, Triart C18 can be presented as an alternative for this type of extreme application.

References: https://www.ymcamerica.com/wp-content/uploads/2026/09/Fast-UHPLC-analyses-of-di-and-tri-peptides-under-challenging-conditions-using-YMC-Triart-C18.pdf  

Currently, the most interesting Triart phases for general peptide applications are YMC-Triart C18, C8, Phenyl, and Bio C18. The two C18 columns are complementary in terms of pore size, with subtle yet significant differences in hydrophobicity. The C8 model provides reduced retention combined with superior steric selectivity due to its higher ligand density, while the Phenyl chemistry completes the selectivity range as an alternative selectivity mode through additional π-π interactions.

References: https://www.ymcamerica.com/wp-content/uploads/2026/09/How-to-choose-the-most-suitable-phenyl-column_0321.pdf 

The unique selectivity and chemical resistance of this group of molecules offers significant exploratory potential and can be applied to all types of biomolecule studies, including the evaluation of degradation products, as demonstrated in the following study on leuprorelin.

References:  https://www.ymcamerica.com/wp-content/uploads/2026/09/Analysis-of-leuprorelin-acetate-using-YMC-Triart-Bio-C18.pdf

References:

WANG, L. et al. Therapeutic peptides: current applications and future directions. Signal Transduction and Targeted Therapy. 2022. https://doi.org/10.1038/s41392-022-00904-4