Chen Buyun, Bartlett Michael G
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352, USA.
Biomed Chromatogr. 2012 Apr;26(4):409-18. doi: 10.1002/bmc.1696. Epub 2011 Sep 6.
Oligonucleotides have developed into highly versatile and selective therapeutics over the past 20 years. More than five discrete mechanisms of action have been reported and more than 10 different chemical modifications have been used to extend their in vivo half-life and reduce their toxicity. Capillary gel electrophoresis (CGE) has been used extensively for the quantitative analysis of oligonucleotide therapeutics in both preclinical and clinical studies since the 1990s. The success of CGE is based on its extraordinary resolving power, which allows for the simultaneous determination of the parent drug and its metabolites. More recently, capillary gel electrophoresis has seen renewed interest with the emergence of replaceable gels with single-base resolving power and new capillary electrophoresis-mass spectrometry interfaces. This review discusses the bioanalysis of therapeutic oligonucleotides showing the evolution of the field over the past two decades leading to the current new approaches. Included in this review are topics such as different gel types, sample introduction modes, sample extraction procedures, separation conditions and detection methods used in CGE, along with discussions of the successes and limitations associated with each.
在过去20年里，寡核苷酸已发展成为用途广泛且具有选择性的治疗药物。已报道了超过五种不同的作用机制，并且使用了十多种不同的化学修饰来延长其体内半衰期并降低其毒性。自20世纪90年代以来，毛细管凝胶电泳（CGE）已广泛用于临床前和临床研究中寡核苷酸治疗药物的定量分析。CGE的成功基于其非凡的分辨能力，这使得能够同时测定母体药物及其代谢物。最近，随着具有单碱基分辨能力的可替换凝胶和新的毛细管电泳-质谱联用接口的出现，毛细管凝胶电泳再次引起了人们的关注。本综述讨论了治疗性寡核苷酸的生物分析，展示了该领域在过去二十年中的发展历程，直至当前的新方法。本综述涵盖的主题包括不同的凝胶类型、进样模式、样品提取程序、CGE中使用的分离条件和检测方法，以及对每种方法的成功之处和局限性的讨论。
