Dieden R, Verbeeck R K, Latinne D, Wallemacq P, Maton N, Lhoest G J
Department of Pharmaceutical Sciences-UCL, Pharmacokinetics and Metabolism Unit-FATC Laboratory of Mass Spectrometry, Brussels, Belgium.
Eur J Drug Metab Pharmacokinet. 1999 Jan-Mar;24(1):83-90. doi: 10.1007/BF03190015.
SDZ-IMM-125 N-methyl leucine 9 hydroxylated in the gamma position is a metabolite which was extracted from incubated human liver microsomes and subsequently separated by normal and reverse-phase HPLC. This metabolite was identified by fast atom bombardment mass spectrometry, electrospray-ms/ms mass spectrometry and nuclear magnetic resonance spectroscopy. The in vitro 50% inhibitory concentration, tested against bidirectional mixed lymphocyte reaction was 80 microg/l indicating that this metabolite does not retain in vitro immunosuppressive activity most probably due to the structural modification of SDZ-IMM-125 in the recognized binding region to cyclophilin A reducing its binding affinity relative to the parent drug.
SDZ-IMM-125在γ位被N-甲基亮氨酸9羟基化，是一种从人肝微粒体孵育物中提取的代谢物，随后通过正相和反相高效液相色谱法进行分离。该代谢物通过快原子轰击质谱、电喷雾串联质谱和核磁共振光谱进行鉴定。针对双向混合淋巴细胞反应测试的体外50%抑制浓度为80微克/升，表明该代谢物不保留体外免疫抑制活性，很可能是由于SDZ-IMM-125在与亲环蛋白A的公认结合区域发生结构修饰，降低了其相对于母体药物的结合亲和力。
