TY - JOUR T1 - Investigation of Figopitant and Its Metabolites in Rat Tissue by Combining Whole-Body Autoradiography with Liquid Extraction Surface Analysis Mass Spectrometry JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 419 LP - 425 DO - 10.1124/dmd.111.043562 VL - 40 IS - 3 AU - Simone Schadt AU - Susanne Kallbach AU - Reinaldo Almeida AU - Jan Sandel Y1 - 2012/03/01 UR - http://dmd.aspetjournals.org/content/40/3/419.abstract N2 - This article describes the combination of whole-body autoradiography with liquid extraction surface analysis (LESA) and mass spectrometry (MS) to study the distribution of the tachykinin neurokinin-1 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 spectrometry identification and semiquantification of parent drug and its metabolites based on LESA-MS. The quality and accuracy of data generated by LESA-MS were assessed in comparison with classic tissue extraction, sample cleanup, and high-performance liquid chromatography 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 semiquantification of figopitant and its metabolites in different tissues and was complementary to quantitative whole-body autoradiography for studying the distribution. ER -