73rd ASMS Conference on Mass Spectrometry and Allied Topics

Nucleoside-based drugs, recognized as purine or pyrimidine analogs, are potent therapeutic agents specifically used for the treatment of viral infections. These drugs exhibit complex interactions with cellular molecular constituents, primarily via activation of phosphorylation cascades leading to consequential interactions with nucleic acids. Determination of nucleoside mono-, di- and triphosphates (NMP, NDP, and NTP) and their deoxy-counterparts (dNMP, dNDP, dNTP), can intuitively reflect the mechanisms of action and efficacy of these drugs.

After administration, ADCs can exist in various forms in the body, including intact ADCs, biotransformation products, free payloads, linker-payload conjugates, and related metabolites. Pharmacokinetic studies of ADCs typically require the assessment of total antibodies, conjugated antibodies, free payloads, drug-to-antibody ratios (DAR), conjugated payloads, drug linkers, relevant metabolites, and the immunogenicity of the ADCs. A variety of bioanalytical platforms are needed to understand the actual role of ADCs in disease, including ELISA, LC-HRMS, and LC-MS/MS.

Topological polar surface area (TPSA) is a calculated value defined as the total surface area of polar atoms (usually oxygen, nitrogen, and attached hydrogen) in a molecule. Experimental polar surface area (EPSA) is different from TPSA, which is determined based on the chromatographic retention of the molecule. EPSA is a key physical property to understand the bioavailability of drugs. In this study, a high-throughput and cost-effective ultra-performance convergence chromatography tandem mass spectrometry (UPCC-MS/MS) assay was developed to understand the permeability of drug candidates.