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.
- analytical chemistry
- distribution
- drug development
- drug disposition
- mass spectrometry
- metabolite identification
- Received November 4, 2011.
- Accepted December 19, 2011.
- The American Society for Pharmacology and Experimental Therapeutics