A model GalNAc-conjugated 16-mer ASO (FLP) and related impurities were provided by AstraZeneca (see Table ). The full sequences can be found in Table . All the GalNAc-conjugates are fully phosphorothioated and comprised of adenosine (A), 5-methylcytosine (MeC), guanine (G), thymine (T) and 2-deoxyribose (d). The related impurities were a singly deaminated FLP (MeC to T) at position 2 from the 5' side (deamination, DA), and FLP with one PS-PO conversion (PO), a longmer comprising an additional dG at the 5' side (N+1), a shortmer having one dG less at the 5' side (N-1), and a FLP for which the dGs and dTs were switched by dTs and dGs, respectively (Switch impurity, non-isobaric). Moreover, a non-conjugated (NC) and a non-conjugated singly deaminated (DA-NC) at the same position as DA were provided by GSK. An 8-mer siRNA comprising of 2 PS linkages, and 2'-modifications (2'-fluoro (f) and 2'-O-methylation (o)) was provided by Novartis. All ONs were dissolved in ACN-water (75:25, v/v) at a concentration of 1 mg/mL for HILIC measurements and in 100% water for AEX and IP-RPLC measurements. The poly(dT) ladder consisting of a 15, 20, 25, 30, and 35-mer was dissolved in 540 µL of ACN-water (75:25, v/v).