Liquid chromatography-based bioanalytical technologies for nucleic acid drugs
- VernacularTitle:基于液相色谱分离技术的核酸类药物生物分析方法研究进展
- Author:
Shumeng SUN
1
;
Lin LIN
1
,
2
;
Daizhou ZHANG
1
,
2
;
Xin LI
3
;
Yongxia GUAN
3
;
Kai CHEN
1
,
2
Author Information
1. Shandong Academy of Pharmaceutical Sciences，Jinan 250101，China
2. Shandong Innovation Center of Engineered Bacteriophage Therapeutics，Jinan 250101，China
3. Lunan Pharmaceutical Group Co.，Ltd.，Shandong Linyi 276000，China
- Publication Type:Journal Article
- Keywords:
nucleic acid drugs;
oligonucleotide;
bioanalysis;
liquid chromatography;
separation technology
- From:
China Pharmacy
2024;35(23):2959-2964
- CountryChina
- Language:Chinese
-
Abstract:
There are three types of bioanalytical methods for nucleic acid drugs， including ligand binding assay， quantitative polymerase chain reaction and liquid chromatography-based bioanalytical technologies. Although the first two assays have high sensitivity， they have poor selectivity and can not differentiate between intact and truncated metabolites. Liquid chromatography- based bioanalytical technologies which are less sensitive， offer high selectivity for the identification of intact and truncated metabolites. They have broad application prospects in both preclinical and clinical investigations of therapeutic nucleic acid drugs. This paper provides a critical review on the characteristics of these technologies and their application to analyze nucleic acid drugs， including high performance liquid chromatography-ultraviolet detection （HPLC-UV）， high performance liquid chromatography- fluorescence （HPLC-FL）， liquid chromatography-tandem mass spectrometry （LC-MS/MS）， liquid chromatography-high resolution- mass spectrometry， microflow liquid chromatography-tandem mass spectrometry （microflow LC-MS/MS） and hybridization liquid chromatography-tandem mass spectrometry. Although these technologies have high sensitivity except for HPLC-UV， they still have some shortcomings， such as suitable probes need to be designed for HPLC-FL， standard substance for LC-MS/MS， and high cost for microflow LC-MS/MS. In addition， the development of some related strategies or technologies （e.g. non-specific adsorption strategy， sample pretreatment） which can improve the sensitivity， has hastened the development of liquid chromatography-based bioanalytical technologies for nucleic acid drugs.
