Single dose pharmacokinetics of aminoglutethimide by a rapid SIM methodology

The kinetics of unchanged aminoglutethimide and of its major metabolite N-acetylaminoglutethimide were investigated in healthy volunteers with a new multiple selected ion monitoring (SIM) technique. This method allows a rapid detection of both the unchanged drug and of its metabolite with a single injection and after minimal handling of the samples. This rapid method provided similar kinetic findings, compared to those described with the more time consuming high pressure liquid chromatographic (HPLC) procedure. Moreover, the SIM method allowed the detection of the N-acetylamino metabolite in plasma at longer time intervals vs. the HPLC method. Some typical features of the kinetic behavior (e.g., a discontinuity in the plasma die-away curve for both unchanged drug and metabolite), attributable to partial liver extraction, could also be more clearly observed with the new procedure. This new, rapid technique confirms that aminoglutethimide and N-acetylaminoglutethimide have very similar plasma die-away curves in subjects with a normal conjugating capacity, and that kinetic patterns or individual blood levels can be readily obtained by SIM with minimal acquisition of supplementary equipment