Single ion monitoring assay for the serotonin re-uptake blocker Org 6582 in plasma

An assay method has been developed to determine the serotonin re-uptake blocker Org 6582 as its free base in plasma. As internal standard an isomer of Org 6582 is used. The assay procedure includes protein precipitation by addition of trichloroacetic acid, n-hexane extraction from basic medium and derivatization with trifluoroacetic acid anhydride. Quantification is performed using gas chromatography mass spectrometry by monitoring the molecular ions of the N-trifluoroacetyl derivatives of Org 6582 and internal standard at m/z 315. The assay method was applied to plasma samples from toxicological and from Phase I clinical studies. The assay characteristics are discussed in relation to comparable assay methods routinely employed in the authors' laboratory to monitor drug levels.