title: Investigation of figopitant and its metabolites in rat tissue by combining whole-body autoradiography with liquid extraction surface analysis mass spectrometry.
abstract: 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.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88400 Biberach an der Riss, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Schadt
authors.forename: Susanne
authors.initials: S
authors.lastname: Kallbach
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Almeida
authors.forename: Jan
authors.initials: J
authors.lastname: Sandel
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000378:metabolism / Q000493:pharmacokinetics*; D001345:Autoradiography / Q000379:methods; D044482:Benzeneacetamides / Q000378:metabolism / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D059625:Liquid-Liquid Extraction / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D064729:Neurokinin-1 Receptor Antagonists; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015320:Tachykinins / Q000037:antagonists & inhibitors; D014018:Tissue Distribution
chemical_list: D000932:Antiemetics; D044482:Benzeneacetamides; D002250:Carbon Radioisotopes; D064729:Neurokinin-1 Receptor Antagonists; D010879:Piperazines; D015320:Tachykinins; C574094:figopitant