Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals

Abstract

In the present study, we developed and validated three liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods for quantification of the agent OL9–116, a Tdp1 inhibitor based on usnic acid, in murine lungs, liver and kidney, respectively. Additionally, a semi-quantitative method was developed for quantification of the agent in the primary tumor node of Lewis lung carcinoma. Tissue samples were prepared using ultrasonic homogenization and QuEChERS methodology. The quantification of the compound was performed using SCIEX 6500 QTRAP mass spectrometer in MRM mode following a chromatographic separation on a C8 reversed-phase column. The methods were validated in terms of selectivity, calibration curve, accuracy, precision, recovery, matrix factor and stability of the prepared sample, and subsequently applied for quantification of the agent OL9–116 in the organs of healthy and tumor-bearing mice following a single intragastric administration of the substance at a dose of 150 mg/kg. A comparison of the distribution of OL9–116 in the organs of the animals demonstrated that the presence of the tumor significantly altered the pharmacokinetics of the substance, reducing its bioavailability, which should be taken into account when developing tumor treatment strategies.