We tested the effect of IPR hydrophobicity on the IP-HILIC impurity profile using a fully PS 16-mer ASO conjugated with GalNAc as a model PS ON pharmaceutical, along with several reference impurities that are commonly encountered after synthesis (see Table ). Notably, each PS ON species comprises over ten thousand potential diastereomers. These compounds were used to test the influence of IPRs on the HILIC retention of the FLP (i), degree of diastereomer separation (ii), the separation between the FLP and the impurities comprising of different (iii) and the same number (iv) of nucleotides, and the separation of the FLP from its non-GalNAc conjugated impurity (v).