铂类抗癌药物及其作用机理的分析技术进展

Analytical Methodologies for the Analysis of Platinum-containing Anticancer Drugs and its Interaction Mechanisms

以顺铂为代表的铂类抗癌药物已投入临床应用将近30年,因强大的抗癌活性及广谱的抗癌效果而得到了迅速发展和广泛应用,卡铂则是另一个成功应用的铂类抗癌药。这些抗癌药的抗癌机理被普遍认为是Pt(Ⅱ)与DNA的亲电作用,进而形成DNA链交联而导致形变,但其详细的作用机理尚未十分清晰。因此,对该类药物的药代动力学、转运机制及作用机理的研究具有重要意义。关于铂族抗癌药物的分离分析方法近年来也得到了飞速的发展,包括测定Pt总量的非选择性方法以及测定未受损Pt化合物的选择性方法。本文综述了研究铂族抗癌药物及其与生物大分子相互作用的分析方法,包括光谱法、电化学方法、高效液相色谱法、气相色谱法、毛细管电泳法、质谱法以及核磁共振法等,主要讨论近十年色谱、质谱技术在铂类抗癌药物分析中的应用特点及不足之处。

Platinum-based anticancer drugs have become one of the leading chemotherapeutic drugs in cancer treatment for over 30 years due to their high level and bread spectrum of antitumor activity. DNA has been identified as a key cellular target of the platinum containing drugs. The crosslinks formed by Pt （II） -DNA interaction lead to DNA twisting and the subsequent cell death, but the mechanism of which is not clarified. Therefore, the understanding of the pharmacokinetics, delivering pathways, mechanism of interacting is of great importance. The analytical strategies for platinum-containing drugs can be classified as selective and non-selective methods. This reviews aims to provide a systematic survey of the latest analytical techniques for the analysis of platinum-containing anticaneer drugs and their interaction with biomolecules. Spectroscopic methods, electroanalytical methods, high-performance liquid chromatography （HPLC）, gas chromatography （GC）, capillary electrophoresis （CE）, mass spectrometry （MS） and others are covered, with the emphasis on chromatographic and mass spectrometric set-ups.