Development and validation of ultra-performance liquid chromatography tandem mass spectrometry methods for the quantitative analysis of the antiparasitic drug DNDI-6148 in human plasma and various mouse biomatrices

by Schouten WM, Van Bocxlaer K, Rosing H, Huitema ADR, Beijnen JH, Kratz JM, Mowbray CE, Dorlo TPC. Journal of Chromatography B 2024, 124377. doi: 10.1016/j.jchromb.2024.124377

Summary: Preclinical pharmacokinetics studies are necessary to evaluate the exposure of Leishmania parasites in the skin to DNDI-6148, a promising new oral drug for the treatment of cutaneous leishmaniasis. The authors of this manuscript developed and validated a reversed phase ultra-performance liquid chromatography coupled to tandem mass spectrometry method to quantify DNDI-6148 in various tissue samples. These samples, including mouse skin, liver and spleen, were homogenized using an enzymatic homogenization workflow, which was nearly 3 times as effective at extracting DNDI-6148 from skin than mechanical homogenization. Protein precipitation yielded reproducible recoveries, with no matrix effects. This method was successfully applied to samples obtained from Leishmania-infected mice, demonstrating its suitability for use in future preclinical research involving DNDI-6148.

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