Calabrese C R, Loadman P M
Clinical Oncology Unit, University of Bradford, West Yorkshire, UK.
J Chromatogr B Biomed Sci Appl. 1997 Mar 7;690(1-2):275-81. doi: 10.1016/s0378-4347(96)00387-8.
The imidazoacridinone C1311 has shown anti-tumour activity both in vitro and in vivo, prompting its acceptance for Phase I clinical trials. A high-performance liquid chromatography method using fluorescence detection has been developed for the analysis of C1311 in mouse and human plasma and mouse tissue samples. This method is selective, sensitive (limit of detection of 1 ng ml-1) and reproducible, with recoveries of > 90%, C1311 was stable over 8 h, at 25 degrees C, in plasma, tumour homogenate, saline and a range of buffers (pH 3.0-8.0). The compound was highly protein bound (> 90%) in plasma which may have important consequences in the pharmacokinetics of the drug.
咪唑并吖啶酮C1311已在体外和体内均显示出抗肿瘤活性，这促使其被批准进入I期临床试验。已开发出一种使用荧光检测的高效液相色谱法，用于分析小鼠和人血浆以及小鼠组织样本中的C1311。该方法具有选择性、灵敏（检测限为1 ng/ml）且可重现，回收率>90%。在25℃下，C1311在血浆、肿瘤匀浆、生理盐水和一系列缓冲液（pH 3.0 - 8.0）中8小时内保持稳定。该化合物在血浆中与蛋白质高度结合（>90%），这可能对药物的药代动力学产生重要影响。
