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.
Footnotes
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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ABBREVIATIONS:
- QWBA
- quantitative whole-body autoradiography
- MS/MS
- tandem mass spectrometry
- MS
- mass spectrometry
- LESA
- liquid extraction surface analysis
- SIM
- single ion monitoring
- NK1
- neurokinin-1
- HPLC
- high-performance liquid chromatography
- ACN
- acetonitrile
- FA
- formic acid
- LSC
- liquid scintillation counting
- CV
- coefficient of variation
- LC
- liquid chromatography
- NSI
- nano-electrospray ionization.
- Received November 4, 2011.
- Accepted December 19, 2011.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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