Evaluation of HPLC Methods for Nucleic Acid Therapeutics

HPLC strategies for nucleic acid therapeutics

核酸类药物分析方法.pdf

This document provides an overview of practical HPLC strategies for nucleic acid therapeutics, with a focus on oligonucleotides, plasmid DNA, and mRNA or other long-chain nucleic acids. It compares the major separation modes used in this field, including reversed-phase, ion-exchange, size-exclusion, and hydrophilic interaction chromatography, and explains their mechanisms, suitable sample types, and analytical strengths. Using representative columns and application examples, it further discusses how ion-pair reagents, salt type, mobile-phase composition, temperature, particle size, and flow rate influence separation performance. The document also summarizes suitable analytical routes for purity evaluation, impurity profiling, fragment distribution, topological isomer analysis, and method screening, making it a useful technical reference for nucleic acid drug development, quality studies, and routine laboratory support.