创新性高分辨质谱技术MALDI-FTMS在小分子药物研发中的应用

MALDI-FTMS emerges as a valuable new high-resolution tool for in-vivo AD-ME-TOX in small molecule R&D

在小分子药物研发中,因临床试验后期出现某些意想不到的结果而导致很多新药研发失败,这无疑是金钱和时间的巨大浪费。作为应对措施,ADME/TOX(吸收、分配、代谢、排泄/毒性)研究现已尽早地整合进入开发进程中,一方面尽可能减少上述局限性,另一方面,便于在进入临床试验之前,掌握有关药物分布、代谢和毒性的重要细节。目前用于确定药物组织分布和代谢产物的定量全身放射自显影激法(QWBA)和液相色谱-质谱法(LC-MS)虽然有用,但并不能提供全面的信息。新型基质辅助激光解吸电离(MALDI)质谱成像(MSI)已经成为合适的技术,许多应用MALDI-TOF和MALDI-FTMS(傅里叶变换质谱仪)的研究显示,通过将QWBA和MALDI MSI等不同方法相结合,可加深对药物的理解,进一步推动它们向市场发展。

In small molecule pharmaceutical R＆D, many potential new drugs fail due to unexpected outcomes late in the clinical trial process - causing huge financial and time set-backs. In response, ADME/TOX （Absorption, Distribution, Metabolism, Excretion/Toxicity） investigations now take place as early as possible to minimize such limitations and to understand essential details of drug distribution, metabolism and toxicology prior to clinical trials. The current methods of determining tissue distribution of drugs and their metabolites - Quantitative Whole Body Autoradiography （QWBA） and Liquid Chromatog-raphy- Mass Spectrometry （LC-MS） - are useful but do not provide the complete picture. A new approach, Matrix Assisted Laser Desorption/Ionization （MALDI） Mass Spectrometry Imaging （MSI） has emerged as a suitable technique, and numer-ous studies using MALDI-TOF and MALDI-FTMS （Fourier Transfer Mass Spectrometry） have shown the power of com-bining methods such as QWBA and MALDI MSI to further drug understanding and market development.