by Schouten WM, Van Bocxlaer K, Rosing H, Huitema ADR, Beijnen JH, Kratz JM, Mowbray CE, Dorlo TPC. Journal of Chromatography B 2025. doi: 10.1016/j.jchromb.2025.124652.
Summary: The authors of this study developed and validated a novel ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method to quantify DNDI-6174, a novel orally active investigational drug with antileishmanial properties, in various murine biomatrices to support translational pharmacokinetic-pharmacodynamic model-informed drug development. Pre-processing of murine tissues with collagenase A was preferable to mechanical disruption. Using human K2EDTA plasma as a surrogate matrix enabled accurate (-12.0%-9.8% bias) and precise (relative standard deviation ≤12.5%) quantification of DNDI-6174. DNDI-6174 was stable under various conditions in all biomatrices investigated. This method was successfully used in a study of the target site pharmacokinetics of DNDI-6174 in a murine cutaneous leishmaniasis skin infection model to support its development as a clinical candidate.
