Evaluating the use of locked nucleic acid capture probes in hybrid LC–MS/MS analysis of siRNA analytes

Agrawal K, Kang L, Ji S, Tena J & Jian W | Bioanalysis, 15(18), 1129-1146, (2023) Keywords: • capture probe • hybridization • LC–MS/MS • locked nucleic acids • oligonucleotides • short interfering RNA (siRNA) Background: Hybrid LC–MS assays for oligonucleotides rely on capture probes to develop assays with high sensitivity and specificity. Locked nucleic acid (LNA) probes are thermodynamically superior to existing capture probes, but are not currently used for hybrid LC–MS assays. Materials & methods: Using two lipid-conjugated double-stranded siRNA compounds as model analytes, hybrid LC–MS/MS assays using LNA probes were developed. Results: The workflows demonstrated the superiority...