title: Determination of nanogram amounts of the antiarrhythmic drug Org 6001 in biological fluids and tissues using selected ion monitoring.
abstract: An assay method has been developed to determine the free base of Org 6001 (3 alpha-amino-5 alpha-androstan-2 beta-ol-17-one . HCl) in biological samples. The assay procedure consists of protein denaturation, ethyl acetate extraction, derivatization with tert-butyldimethylchlorosilane in dimethylformamide followed by n-hexane extraction and selected ion monitoring using trideuterated Org 6001 as an internal standard. For quantitation, the signals were monitored corresponding to the masses of the [M - 57]+ ions of 2-O-tert-butyldimethylsilyl, N-formyl derivatives of Org 6001 and the internal standard at m/z 390 and m/z 393, respectively. The assay method was applied to plasma samples from the human and rat, and to rat tissues including the target organ, the heart. The relationship between the Org 6001 plasma level and clinical effect in the human, the distribution of Org 6001 in rat tissues, and the correlation between the plasma level and the amount of Org 6001 in total heart tissue of the rat were determined.
mesh_terms: D000732:Androstanols / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000032:analysis*; D001145:Arrhythmias, Cardiac / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007700:Kinetics; D008832:Microchemistry; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000732:Androstanols; D000889:Anti-Arrhythmia Agents; C010158:amafolone