Overcoming Challenges in Oligonucleotide Therapeutics Analysis: A Novel Nonion Pair Approach

Oligonucleotide therapeutics (OT) have emerged as promising drug modality for various intractable diseases. Recently, liquid chromatography–mass spectrometry (LC-MS) has been commonly employed for characterizing and quantifying OT in biological samples. Traditionally, the ion pairing–reverse phase (...

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Published inJournal of the American Society for Mass Spectrometry Vol. 35; no. 9; pp. 2034 - 2037
Main Authors Hayashi, Yoshiharu, Sun, Yuchen
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 04.09.2024
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ISSN1044-0305
1879-1123
1879-1123
DOI10.1021/jasms.4c00270

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Summary:Oligonucleotide therapeutics (OT) have emerged as promising drug modality for various intractable diseases. Recently, liquid chromatography–mass spectrometry (LC-MS) has been commonly employed for characterizing and quantifying OT in biological samples. Traditionally, the ion pairing–reverse phase (IP-RP) LC-MS method has been utilized in OT bioanalyses; however, this approach is associated with several limitations, including the memory effect and ion suppression effect of IP reagents. Therefore, this study aimed to develop a new RP-LC-MS method that eliminates the need for IP reagents. Our investigation revealed that ammonium bicarbonate was essential for the successful implementation of this nonIP-RP-LC-MS-based bioanalysis of OT. Moreover, the developed method demonstrated high versatility, accommodating the analysis of various natural or chemically modified oligonucleotides. The sensitivity of the method was further assessed using reconstituted plasma samples (the lower limit of quantification in this experiment was 0.5–1 ng/mL). In summary, the developed nonIP-RP-LC-MS method offers an easy, reliable, and cost-effective approach to the bioanalysis of OT.
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ISSN:1044-0305
1879-1123
1879-1123
DOI:10.1021/jasms.4c00270