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色谱法测定治疗性寡核苷酸。

Chromatographic methods for the determination of therapeutic oligonucleotides.

机构信息

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2352, USA.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Feb 1;883-884:76-94. doi: 10.1016/j.jchromb.2011.09.007. Epub 2011 Sep 10.

DOI:10.1016/j.jchromb.2011.09.007
PMID:21945211
Abstract

Both DNA and RNA are being explored for their therapeutic potential against a wide range of diseases. As these new drugs emerge, new demands arise for the analysis and quantitation of these biomolecules. Pharmacokinetic and pharmacodynamic analysis requirements for drug approval place enormous challenges on the methods for analyzing these therapeutics. This review will focus on bioanalytical methods for DNA antisense and aptamers as well as small-interfering RNA (siRNA) therapeutics. Chromatography methods employing ultraviolet (UV), fluorescence and mass spectrometric (MS) detection along with matrix-assisted laser desorption/ionization (MALDI) will be covered. Sample preparation from biological matrices will be reviewed as well as metabolite analysis and identification. All of these techniques are important contributions toward oligonucleotide therapeutic development. They will also be important in microRNA (miRNA) biomarker discovery and RNomics in general, as more non-coding RNAs are inevitably discovered.

摘要

DNA 和 RNA 都在被探索其在治疗多种疾病方面的潜力。随着这些新药的出现,对这些生物分子的分析和定量提出了新的要求。药物批准的药代动力学和药效学分析要求对这些疗法的分析方法提出了巨大的挑战。本文将重点介绍 DNA 反义寡核苷酸和适体以及小干扰 RNA(siRNA)治疗药物的生物分析方法。将涵盖采用紫外(UV)、荧光和质谱(MS)检测以及基质辅助激光解吸/电离(MALDI)的色谱方法。还将回顾从生物基质中进行样品制备以及代谢物分析和鉴定。所有这些技术都是寡核苷酸治疗开发的重要贡献。随着越来越多的非编码 RNA 不可避免地被发现,它们在 miRNA 生物标志物发现和一般的 RNomics 中也将非常重要。

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