A sensitive and rapid liquid chromatography-tandem mass spectrometry method for the quantification of the novel neurokinin-1 receptor antagonist aprepitant in rhesus macaque plasma, and cerebral spinal fluid, and human plasma with application in translational NeuroAIDs research

Di Wu, Dustin J. Paul, Xianguo Zhao, Steven D. Douglas, Jeffrey S. Barrett

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

A sensitive and rapid liquid chromatography-tandem mass spectrometry method has been developed for to assess therapeutic exposures of aprepitant in HIV-infected patients and rhesus macaques. The method utilized a simple sample-preparation procedure of protein precipitation with methanol. Chromatographic separation was performed on a reversed phase C8 column (Hypersil Gold, 50 mm × 2.1 mm, 3 μm) using a mobile phase composed of acetonitrile and water in 0.5% formic acid through gradient elution. Electro-spray ionization in positive mode was incorporated in the tandem mass spectrometric detection. The lower limit of quantitation of aprepitant in plasma of rhesus macaques and human and cerebral spinal fluid of rhesus macaques were 1, 1, and 0.1 ng/mL, respectively. The method has been successfully employed to measure aprepitant in preclinical and clinical samples collected from three SIV-infected rhesus macaques and ten patients with HIV infection. In conclusion, this liquid chromatography-tandem mass spectrometry method is suitable for preclinical-clinical translational research exploring exposure-response relationships with aprepitant as well as therapeutic drug monitoring of aprepitant.

Original languageEnglish (US)
Pages (from-to)739-745
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume49
Issue number3
DOIs
StatePublished - Apr 5 2009

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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