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Determination of 2'-beta-fluoro-2',3'-dideoxyadenosine, an experimental anti-AIDS drug, in human plasma by high-performance liquid chromatography.

Abstract
2'-Beta-fluoro-2',3'-dideoxyadenosine (F-ddA, lodenosine) is an experimental anti-AIDS drug currently being evaluated in a Phase I clinical trial. A simple and specific HPLC method with UV detection, suitable for use in clinical studies, has been developed to determine both F-ddA and its deaminated catabolite, 2'-beta-fluoro-2',3'-dideoxyinosine (F-ddI) in human plasma. After inactivation of plasma HIV by 0.5% Triton X-100, the compounds of interest are isolated and concentrated using solid-phase extraction. Processed samples are separated by use of a pH 4.8 buffered methanol gradient on a reversed-phase phenyl column. The method has a linear range of 0.05-5 microg/ml (0.2-20 microM) and intra-assay precision is better than 8%. Analyte recovery is quantitative and plasma protein binding is minimal. In addition, drug and metabolite levels measured in Triton-treated human plasma remain stable for at least 5 months when samples are stored frozen without further treatment. Compound concentrations determined after samples are processed and then frozen for up to 1 month before analysis are also unchanged.
AuthorsJ S Roth, H Ford Jr, M Tanaka, H Mitsuya, J A Kelley
JournalJournal of chromatography. B, Biomedical sciences and applications (J Chromatogr B Biomed Sci Appl) Vol. 712 Issue 1-2 Pg. 199-210 (Aug 07 1998) ISSN: 1387-2273 [Print] Netherlands
PMID9698243 (Publication Type: Journal Article)
Chemical References
  • Anti-HIV Agents
  • Blood Proteins
  • lodenosine
  • Dideoxyadenosine
Topics
  • Acquired Immunodeficiency Syndrome (blood, virology)
  • Anti-HIV Agents (blood, metabolism)
  • Blood Proteins (metabolism)
  • Chromatography, High Pressure Liquid
  • Dideoxyadenosine (analogs & derivatives, blood, metabolism)
  • Drug Stability
  • HIV (drug effects, growth & development)
  • HIV Seropositivity (blood, virology)
  • Humans
  • Protein Binding
  • Reproducibility of Results
  • Spectrophotometry, Ultraviolet

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