A rapid and green analytical strategy to determine menin inhibitor revumenib in human blood serum via CE-DAD

Abstract

Revumenib (formerly SNDX-5613) is a novel, potent and oral menin inhibitor employed in clinical settings because of treating acute myeloid leukemia in critically ill patients. Nevertheless, safety is still a matter of concern due to the optimal timing of administration and doses of this anticancer agent. An effective tool that allows to solve the drug dosage regimen is therapeutic drug monitoring. In that sense, simple, sensitive and accurate bioanalytical strategies are required. Here, a rapid capillary electrophoresis with diode-array detector methodology was developed and applied for the first time to detect, identify and determine revumenib in complex clinical matrices such as human blood serum in less than 5 min of analysis with a minimal sample preparation procedure based on a protein precipitation with acetonitrile. Various chemical and instrumental critical parameters were rigorously optimized for the separation process in a fused-silica capillary with a background electrolyte of phosphate buffer (50 mM, pH = 2.0) in deionized water. Adequate analytical performance parameters were obtained involving a good linearity, detection and quantification limits at ng mL⁻¹ levels, and a correct precision and accuracy. Furthermore, this approach can be characterized as an ecofriendly strategy in the bioanalysis field based on an estimated greenness evaluation via AGREEprep and AGREE metrics tool with acceptable scores. Considering the results, the present work can be used as a new medical tool and successfully applied in the therapeutic monitoring of revumenib in routine clinical laboratories but also to take appropriate decisions in future (pre)clinical trials and/or phases.