A UPLC-MS/MS assay for the quantification of the novel viral helicase-primase drug candidate adibelivir (IM-250) in human specimen

Adibelivir (IM-250) is a novel helicase-primase inhibitor under development for the treatment of herpes simplex virus infections. A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was established for the quantification of adibelivir in human plasma and urine samples of a first-in-human clinical trial using a deuterated internal standard. This assay was validated based on the pertinent ICH M10 guideline for the linear range of 1-1000 ng/mL. The method fulfilled all criteria with a high inter-run accuracy of 100.0-101.4% and inter-run precision of 2.96-10.5%. The feasibility of the assay was shown for two healthy individuals by evaluating their pharmacokinetics of adibelivir. Additionally, the assay was adapted for the quantification of adibelivir in urine with a lowered calibration range of 0.1-100 ng/mL. The present work provides a fully validated assay for pharmacokinetic analyses of adibelivir in clinical development, e.g. in its first-in-human phase I trial (EudraCT 2022-003679-40).