A pilot study on the use of laser ablation-ICP-mass spectrometry for assessing/mapping the distribution of a drug and its metabolites across the body compartments of rats

Abstract

Application of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) has been studied as an alternative to radioluminography (RLG) for assessing the distribution of a novel anti-tuberculosis compound containing bromine as a “hetero-element” and its metabolites over the body compartments of rat, used as a test animal. In contrast to RLG, LA-ICP-MS does not require labeling of the drug compound with a radionuclide. After administration of the Br-containing drug and a sufficient delay time to allow drug uptake and distribution, the sacrificed animal was frozen and embedded in carboxymethyl cellulose (CMC), after which thin sections were obtained using a microtome. For quantification purposes, hardened gelatin films on a glass support were used as “matrix-matched” Br standards. The limit of detection (LOD) for Br estimated using one of these in-house made standards was 0.1 μg g⁻¹, which is sufficiently low to allow visualization of Br in the main organ of interest (lung). LA-ICP-MS analysis via single spot drilling with a wider laser beam diameter on the organ of interest was performed as well. In this case, quantification was accomplished via external calibration versus droplets of standards containing the pure drug that were co-embedded with the rat. Figures of merit achievable with LA-ICP-MS were critically evaluated and compared to those typical for the traditional technique, based on the use of radionuclides.