Laboratory Testing Case Studies

Challenge: A sponsor had developed a promising group of "first in class" potent small molecule compounds for cancer therapy.  The research scientists and medicinal chemists used structure-based drug design to derive compounds that target important proteins and therapeutic pathways in cancer.  One of these candidates has shown to be a very potent, yet highly selective growth inhibitor of many cancer types, including non-small cell lung cancer, colon cancer and leukemia.

Challenge: The goal of this work was to investigate the improvement of resolution between all multimer, dimer and monomers in a monoclonal antibody (mAb).  The method was initially developed by the sponsor but failed to demonstrate adequate level of sensitivity and selectivity when used during stability studies.  In addition the resolution between the analytes (monomer, dimer and multimer) was very poor.

Challenge: Typical oligonucleotides used as therapeutics or potential therapeutic compounds are 15 to 30 nucleotides (nt) long. Oligonucleotides <15 nt can be readily resolved by HPLC technology, however the separation of longer sequences are more challenging. Ion-pair reversed-phase (IP-RP) HPLC has been traditionally used for oligonucleotides analysis.  The traditional IP-RPLC eluent system typically uses TEA or TEAA or HFIP and the ion-pairing agent triethylammonium ion and a C18, column at 60^oC. Under such conditions, the column's hydrolytic stability becomes crucial and is important to prevent the potential contribution of the oligonucleotide secondary structure from impacting retention.