Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
J Pharm Biomed Anal. 2011 Jun 1;55(3):540-3. doi: 10.1016/j.jpba.2011.02.014. Epub 2011 Feb 17.
The changes in concentration of kynurenic acid (KYNA) in different biological samples are of great interest in the pathomechanism and medication of several disorders, and especially those affecting the nervous system. Besides the recent pharmaceutical advances targeting the kynurenine pathway, there is a constant need for further drug development through the synthesis of novel analogs. Reliable analytical methods should be set up to monitor the metabolism and effects of these analogs in both preclinical experiments and human studies. Following a sample preparation procedure based on protein precipitation, new high-performance liquid chromatographic methods with fluorescence and mass spectrometric detection were developed for the determination of KYNA and a novel KYNA analog (N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride; KYNA amide) in mouse serum samples. The analytical parameters obtained in the validation procedure suggest that the developed method with mass spectrometric detection is simple, fast, accurate and suitable for the measurement of KYNA and its analogs. The results reveal the good in vivo stability of the novel KYNA amide.
犬尿氨酸(KYNA)在不同生物样本中的浓度变化在几种疾病的发病机制和药物治疗中,尤其是在影响神经系统的疾病中,具有重要意义。除了最近针对犬尿氨酸途径的药物进展外,还需要通过合成新的类似物来不断进行药物开发。应该建立可靠的分析方法,以监测这些类似物在临床前实验和人体研究中的代谢和作用。在基于蛋白质沉淀的样品制备程序之后,开发了新的用于测定 KYNA 和一种新型 KYNA 类似物(N-(2-N,N-二甲基氨基乙基)-4-氧代-1H-喹啉-2-甲酰胺盐酸盐;KYNA 酰胺)的高效液相色谱法,具有荧光和质谱检测。在验证程序中获得的分析参数表明,具有质谱检测的开发方法简单、快速、准确,适用于 KYNA 及其类似物的测定。结果表明,新型 KYNA 酰胺具有良好的体内稳定性。