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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 the research and development of small molecule drugs, many new drugs failed to be developed due to some unexpected results in the late phase of clinical trials, which is undoubtedly a huge waste of money and time. As a response, research on ADME / TOX (absorption, distribution, metabolism, excretion / toxicity) has now been integrated into the development process as soon as possible to minimize the above limitations on the one hand and to facilitate access to clinical trials Important details about the distribution, metabolism and toxicity of drugs. Quantitative whole-body autoradiography (QWBA) and liquid chromatography-mass spectrometry (LC-MS), currently used to determine the distribution of tissue and metabolites, are useful, but do not provide comprehensive information. New matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) has become a suitable technique and many studies using MALDI-TOF and MALDI-FTMS (Fourier Transform Mass Spectrometry) show that by using different methods such as QWBA and MALDI MSI The combination can deepen the understanding of drugs and further promote their development to the market.