LC/MS技术在寡核苷酸类药物生物样品定量分析和代谢物鉴定中的应用  

Quantitative Analysis and Metabolite Identification of Therapeutic Oligonucleotides in Biological Samples Using LC/MS

作　　者：邓泮[1] 钟大放[1] 陈笑艳[1] 

机构地区：[1]中国科学院上海药物研究所,上海201203

出　　处：《质谱学报》2011年第1期13-23,30,共12页Journal of Chinese Mass Spectrometry Society

摘　　要：寡核苷酸是药物发展的新领域，这类药物是人工合成的DNA或RNA片段，一般由15～50个核苷酸组成，其药动学研究的经典方法是酶联免疫法，但由于该方法的建立耗时、耗资，因此成为新药研发的瓶颈。液相色谱一质谱（LC／MS）联用技术在寡核苷酸类药物生物分析中面临的主要问题有：待测物离子化效率低、基质效应严重、色谱分离条件与质谱不易兼容，样品处理回收率低，但该方法建立快速且选择性强，并能够同时进行代谢产物研究，因此，这项技术尽管存在一些缺点但依然备受关注。本文综述了过去15年中LC／MS技术在寡核苷酸类药物生物样品定量分析和代谢物鉴定中的发展和应用。Therapeutic oligonucleotides have become as a new drug class. They are synthetic DNA or RNA that typically between 15 and 50 nucleotide units long. In the pharmacokinetic studies of therapeutic oligonucleotides, the classical method was enzyme-linked immunosorbent assay （ELISA）. However, the development of ELISA method was time-consuming and expensive, and has become the bottleneck in the new drug research and development. The technical issues associated with liquid chromatography-mass spectrometry （LC/ MS） method in the bioanalysis of oligonucleotides included： limited ionization efficiency, severe matrix effect, incompatibility of chromatographic condition and MS detection, and low sample preparation recovery. However, the development of an LC/MS method was fast, and this method was selective. This review summarized the development and applications of LC/MS method for the quantitation of therapeutic oligonucleotides and characterization of their metabolites in biological samples described in the literatures over the past 15 years.

关 键 词：寡核苷酸药物 液相色谱-质谱联用 生物样品 

分 类 号：O657.63[理学—分析化学]