Abstract

This contribution describes the combination of whole body autoradiography with liquid extraction surface analysis (LESA) and mass spectrometry (MS) to study the distribution of the tachykinin NK₁ antagonist figopitant and its metabolites in tissue sections of rats after intravenous administration of 5.0 mg/kg figopitant. An overview of autoradiography results is presented together with mass spectrometric identification and semi-quantification of parent drug and its metabolites based on LESA-MS. The quality and accuracy of data generated by LESA-MS was assessed by comparison to classical tissue extraction, sample cleanup and HPLC analysis. The parent drug and the N-dealkylated metabolite M474(1) (BIIF 1148) in varying ratios were the predominant compounds in all tissues investigated. In addition, several metabolites formed by oxygenation, dealkylation, and a combination of oxygenation and dealkylation were identified. In summary, the LESA-MS technique was shown to be a powerful tool for identification and semi-quantification of figopitant and its metabolites in different tissues and was complementary to quantitative whole-body autoradiography (QWBA) for studying the distribution.