Validated LC-MS/MS method for quantifying the antiparasitic nitroimidazole DNDI-0690 in preclinical target site PK/PD studies

by Schouten WK, van Bocxlaer H, Rosing H, Huitema ADR, Beijnen JH, Kratz JM, Mowbray CE, Dorlo TPC. Biomedical Chromatography 2025, 39(8): e70158. doi: 10.1002/bmc.70158

Summary: It is important to understand the target site pharmacokinetics of potential treatments for leishmaniasis, because of the diversity of infected tissue sites and potential variability in drug penetration. The authors of this manuscript developed and validated an ultrahigh-performance liquid chromatography-tandem mass spectrometry method to quantify the nitroimidazole analog DNDI-0690 in various murine biomatrices. Efficient and reproducible tissue homogenization and extraction of DNDI-0690 were achieved using collagenase A-based enzymatic homogenization, followed by protein precipitation for sample clean-up, resulting in a reproducible overall recovery without significant matrix effects. DNDI-0690 remained stable in all biomatrices under various conditions. This method was successfully used to quantify DNDI-0690 in a murine infection model, demonstrating its suitability for future target site pharmacokinetics studies involving DNDI-0690.

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