biostudies-literatureUnknown97(36)Song ZSmall interfering RNA (siRNA) is a new class of oligonucleotide therapeutics that is rapidly growing in drug research and development for the treatment of various diseases. One major challenge for siRNA therapeutics is their inefficient delivery to target tissues by systemic administration. Antibody-siRNA conjugates (ARC) are being developed as a promising approach to enhancing the selectivity and delivery of siRNA payloads to target tissues. A sensitive, selective, and reliable method to quantify ARCs in biological samples is critical to understand their pharmacokinetics, pharmacodynamics, toxicity, and biodistribution properties. There are very limited methods reported for the quantification of ARCs, including reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or hybrAnalytical chemistry19570-19577https://www.ebi.ac.uk/biostudies/studies/S-EPMC12444745biostudies-literatureA Novel Hybrid LC-MS/MS Methodology for the Quantitative Bioanalysis of Antibody-siRNA Conjugates.PMC12444745Yuan LSong ZfalseA Novel Hybrid LC-MS/MS Methodology for the Quantitative Bioanalysis of Antibody-siRNA Conjugates.Small interfering RNA (siRNA) is a new class of oligonucleotide therapeutics that is rapidly growing in drug research and development for the treatment of various diseases. One major challenge for siRNA therapeutics is their inefficient delivery to target tissues by systemic administration. Antibody-siRNA conjugates (ARC) are being developed as a promising approach to enhancing the selectivity and delivery of siRNA payloads to target tissues. A sensitive, selective, and reliable method to quantify ARCs in biological samples is critical to understand their pharmacokinetics, pharmacodynamics, toxicity, and biodistribution properties. There are very limited methods reported for the quantification of ARCs, including reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or hybr2025-01-01T00:00:00Z2025 Sep2026-06-03T14:32:20.514Z2026-04-28T03:11:11.084ZS-EPMC124447454088841610.1021/acs.analchem.5c02727