In Vivo Metabolite Profiles of a GalNAc Conjugated Antisense Oligonucleotide AZD8233 Using Liquid Chromatography-High Resolution Mass Spectrometry: a Cross Species Comparison in Animals and Humans

• Published in: Drug metabolism and disposition
• Main Authors: Li, Xue-Qing, Elebring, Marie, Dahlén, Anders, Weidolf, Lars
• Format: Journal Article
• Language: English
• Published: United States 10.07.2023
• Subjects: human/clinical; High performance liquid chromatography (HPLC); animal/nonclinical/preclinical; Mass spectrometry (MS); antisense oligonucleotides; drug metabolism; metabolite identification

AZD8233, a liver-targeting antisense oligonucleotide (ASO), inhibits subtilisin/kexin type 9 protein synthesis. It is a phosphorothioated 3-10-3 gapmer with a central DNA sequence flanked by constrained 2'- -ethyl 2',4'-bridged nucleic acid (cEt-BNA) wings and conjugated to a trianten...