Sirtori C R, De Fabiani E, Caruso D, Malavasi B, Galli G, Galli-Kienle M
Niguarda Ca' Granada Hospital, University of Milano, Milano, Italy.
Int J Clin Pharmacol Ther Toxicol. 1988 Aug;26(8):380-4.
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.
采用一种新的多选择离子监测（SIM）技术，在健康志愿者中研究了未变化的氨鲁米特及其主要代谢物N - 乙酰氨鲁米特的动力学。该方法通过单次注射并在对样品进行最少处理后，能够快速检测出未变化的药物及其代谢物。与耗时更长的高压液相色谱（HPLC）方法相比，这种快速方法得出了相似的动力学结果。此外，与HPLC方法相比，SIM方法能够在更长的时间间隔检测出血浆中的N - 乙酰氨基代谢物。由于部分肝脏提取导致的动力学行为的一些典型特征（例如，未变化的药物和代谢物的血浆消除曲线中的不连续性），通过新方法也能更清晰地观察到。这种新的快速技术证实，在具有正常结合能力的受试者中，氨鲁米特和N - 乙酰氨鲁米特具有非常相似的血浆消除曲线，并且通过SIM能够轻松获得动力学模式或个体血药浓度，同时只需最少的辅助设备购置。
