Post by Kui Yang

🎉 Excited to share our latest publication in Analytical Chemistry! 🎉 "Decoding Oligonucleotide Stereochemistry: Individual Phosphorothioate Configuration Ratios and Intact Sequence Diastereomeric Composition" https://lnkd.in/g7NtAUz9 Characterizing the stereochemical complexity of PS-modified oligonucleotides in finished products has remained one of the field’s greatest analytical challenges, with direct implications for drug development, batch-to-batch consistency, and generic product sameness assessment. In this work, we present a high-resolution ion mobility mass spectrometry (HRIM-MS) approach that, for the first time, simultaneously measures within the same complete 3-mer sequence: 🔹Intact sequence diastereomeric composition 🔹Individual PS linkage Rp/Sp configuration ratios. A key finding: The intact diastereomeric composition can deviate from what would be predicted by simple statistical combinations of individual PS configuration ratios, highlighting potential risks: batches with similar individual PS Rp/Sp ratios may exhibit substantially different intact sequence diastereomeric profiles, with potential implications for therapeutic performance and product comparability. #FDA #Oligonucleotide #MassSpectrometry #IonMobility #DrugQuality #GenericDrugs