Validation and Application of Hybridization Liquid Chromatography-Tandem Mass Spectrometry Methods for Quantitative Bioanalysis of Antisense Oligonucleotides

• DOI: 10.4155/bio-2022-0015
• Publication Date: 2022-05-12T09:22:06Z
• Authors: Pei Li; Jean-François Dupuis; Valerie Vrionis; Kevork Mekhssian; Tom Magee; Long Yuan
• Keywords: Bioanalysis; Matrix (chemical analysis)

Background: Antisense oligonucleotide (ASO), an emerging modality in drug research and development, demands accurate sensitive bioanalysis to understand its pharmacokinetic pharmacodynamic properties. Results: By combining the advantages of both ligand binding liquid chromatography-mass spectrometry/tandem mass (LC-MS/MS), hybridization LC-MS/MS methods were successfully developed validated/qualified a good lab practice (GLP) environment for quantitation ASO candidate monkey serum, cerebrospinal fluid (CSF) tissues range 0.5-500 ng/ml. Special treatment CSF samples was employed mitigate nonspecific binding, improve long-term storage stability enable usage artificial as more accessible surrogate matrix. The method also qualified applied various tissue using cocktail homogenate Conclusion: This work first reported GLP validation application platform.