OliPharma Develops Stereomer Detection Method for Oligonucleotide Therapeutics to Support Regulatory Submissions

In oligonucleotide drugs, antisense oligonucleotides (ASOs) often utilize full phosphorothioate modifications, resulting in a higher number of diastereomers, complex compositions, and making the complete analysis and identification of their PS isomers difficult to achieve.Compared with ASO, small interfering RNA (siRNA) has relatively fewer phosphorothioate modifications, making the composition and analysis of its diastereomers more feasible.Taking the marketed drug Inclsirian (Inclisiran sodium) as an example, its sense strand has 4 isomers, its antisense strand has 16 isomers, and the double strands have a total of 20 stereoisomers.

To address the challenges of stereoisomer analysis in siRNA drug registration submissions,Olipharma used Inlcisiran as the research object and denatured IPRP-HPLC as the analytical method. By optimizing conditions such as ion-pair reagents, mobile phase composition, ratio, gradient, and column temperature, they successfully achieved effective separation and detection of stereoisomers in siRNA oligonucleotide drugs.