title: Measurement of rimantadine in plasma by capillary gas chromatography/mass spectrometry with a deuterium-labeled internal standard.
abstract: Rimantadine is a synthetic antiviral agent used in prophylaxis and in treating the early stages of uncomplicated influenza A illness. We describe a stable isotope-dilution assay involving capillary gas chromatography/mass spectrometry. We used 200 ng of d3-rimantadine, added to 1 mL of plasma, as the internal standard. The rimantadine was extracted from the plasma with a Bond-Elut CN column, the column was washed with water, and the rimantadine was eluted with methanol, dried, and treated to form the t-butyldimethylsilyl derivative. The mass spectrometer was operated in the selected ion monitoring mode. Ions at m/z 236 and m/z 239 were monitored, corresponding to the loss of C4H9 from the rimantadine derivative and d3-rimantadine, respectively. Within-run precision (CVs) ranged from 8.9% at 29 micrograms/L to 3.2% at 1666 micrograms/L. Corresponding data for between-run precision were 5.4% and 1.7%. Treated volunteers (n = 86) provided plasma samples with a concentration range of 153 to 1127 micrograms/L. This simplified method allows rapid, precise assay of rimantadine in plasma.
authors.affiliation: Department of Pathology, University of Virginia Medical Center, Charlottesville 22908.
authors.forename: D A
authors.initials: DA
authors.lastname: Herold
authors.forename: P K
authors.initials: PK
authors.lastname: Anonick
authors.forename: M
authors.initials: M
authors.lastname: Kinter
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives*; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D012299:Rimantadine / Q000097:blood*
chemical_list: D012299:Rimantadine; D003903:Deuterium; D000218:Adamantane