Determination of rimantadine and its hydroxylated metabolites in human plasman and urine

Abstract 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 measured were between 25-1250, 25-500 and 12.5-250 ng/ml, respectively.