演題概要

1P-46

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TOF-MSによる合成オリゴヌクレオチド中の不純物解析のためのワークフロー

(¹日本ウォーターズ・ ²ウォーターズ)
^o矢田絵都子¹・ 寺崎真樹¹・ Delaney, Kellen²・ Riley, Jo-Anne²・ Fox, Jonathan²・ Gastall, Heidi²・ Denbigh, Laetitia²・ Yu, Ying Qing²・ Pittman, Nick²・ Berger, Scott²・ 廣瀬賢治¹

Nucleic acid therapeutics have gained substantial interest in recent years. Synthetic oligonucleotides are a class of nucleic acid therapeutics that are attractive for their ability to selectively target specific genes. While oligonucleotides are synthesized, they can introduce impurities that may affect their safety and efficacy. As the length and complexity of the synthetic oligonucleotide increases, the complexity of the impurity profile also increases.
We developed impurity workflow using ion pair reversed chromatography mode Ultra-performance chromatography-time of flight mass spectrometer (UPLC-TOF MS) and an integrated informatics platform was developed to streamline oligonucleotide analysis. The workflow automated several data review steps to expedite data analysis, such as system suitability checks, injection repeatability evaluation, calibration curve generation, and soft-vs-harsh ionization comparison. To detect and quantify impurities in Nusinersin, a component list containing the full-length product (FLP) and 16 impurities was imported into the analysis method. Report templates were created to distill the large volume of information into a simplified document that summarizes the key information from each analysis. The complete workflow reduced data analysis time from hours to minutes and is readily amended for different synthetic oligonucleotides and impurity lists without LC-MS expertise.