Determination of rimantadine and its hydroxylated metabolites in human plasma and urine.
A gas chromatographic-mass spectrometric procedure has been developed for the quantitation of the antiviral agent rimantadine and its meta- and para-hydroxylated metabolites in human plasma and urine. The assay utilizes an extractive pentafluorobenzoylation at alkaline pH with cyclohexane saturated with triethanolamine-chloroform (2:1) containing pentafluorobenzoyl chloride, selective ion monitoring, methane negative ion chemical ionization mass spectrometry and stable isotope dilution. The method has been used to measure plasma concentrations of rimantadine, m-hydroxyrimantadine and the two epimers of p-hydroxyrimantadine between 5-250, 5-100 and 2.5-50 ng/ml, respectively. Similarly, the urine concentrations of these analytes measured were between 25-1250, 25-500 and 12.5-250 ng/ml, respectively.
Rubio
F A
FA
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Choma
N
N
Fukuda
E K
EK
D000218:Adamantane / Q000031:analogs & derivatives*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D012299:Rimantadine / Q000097:blood / Q000378:metabolism* / Q000652:urine
D012299:Rimantadine; D000218:Adamantane