A validated capillary microsampling liquid chromatography-tandem mass spectrometry method for quantification of antisense oligonucleotides in mouse serum

Background: Capillary microsampling (CMS) has been used for quantitative bioanalysis of small molecules; however, there is no report of applying this technique in the bioanalysis of antisense oligonucleotides (ASOs). Results: A CMS liquid chromatography-tandem mass spectrometry method was successfully developed and validated for the quantification of ASO1 in mouse serum. The validated method was applied in a safety study in juvenile mice. Equivalent performance between CMS samples and conventional samples was demonstrated in the mouse study. Conclusion: This work is the first to report using CMS for liquid chromatography-tandem mass spectrometry quantitative bioanalysis of ASOs. The validated CMS method was successfully applied to support good laboratory practice safety studies in mice and the CMS strategy has subsequently been applied to other ASOs.

Automated summary

This study is the first to report the use of capillary microsampling (CMS) for quantitative bioanalysis of antisense oligonucleotides (ASOs) using liquid chromatography-tandem mass spectrometry. The developed method was successfully validated and applied in a safety study in mice, demonstrating equivalent performance between CMS samples and conventional samples. The utility of CMS strategy has further been applied to other ASOs.