BIOANALYSIS AND BIOTRANSFORMATION OF OLIGONUCLEOTIDE THERAPEUTICS BY LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY
James Michael Sutton1, Jaeah Kim1, Noha M El Zahar1,2
1Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, 250 West Green Street, Athens, GA, 30602-2352.
Abstract:
Since 2016, eight new oligonucleotide therapies have been approved which has led to increased interest in oligonucleotide analysis. There is a particular need for powerful bioanalytical tools to study the metabolism and biotransformation of these molecules. This review provides the background on the biological basis of these molecules as currently used in therapies. The article also reviews the current state of analytical methodology including state of the art sample preparation techniques, liquid chromatography-mass spectrometry methods, and the current limits of detection/quantitation. Finally, the article summarizes the challenges in oligonucleotide bioanalysis and provides future perspectives for this emerging field. © 2020 John Wiley & Sons Ltd.
Insights
New oligonucleotide therapies require advanced bioanalytical methods for studying their metabolism and biotransformation. This review covers analytical techniques and challenges in oligonucleotide analysis.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Pharmacology
Background:
- Eight new oligonucleotide therapies approved since 2016 have increased interest in their analysis.
- Oligonucleotide-based therapeutics are gaining prominence in various medical fields.
- Understanding the metabolism and biotransformation of these drugs is crucial for their effective use.
Purpose of the Study:
- To provide a comprehensive overview of oligonucleotide analysis.
- To review current analytical methodologies for studying oligonucleotide metabolism.
- To identify challenges and future perspectives in the field of oligonucleotide bioanalysis.
Main Methods:
- Review of existing literature on oligonucleotide therapies and bioanalytical techniques.
- Discussion of sample preparation methods relevant to oligonucleotide analysis.
- Overview of liquid chromatography-mass spectrometry (LC-MS) applications in oligonucleotide quantification.
Main Results:
- Current analytical methods, including sample preparation and LC-MS, are discussed.
- The review highlights the state-of-the-art in detecting and quantifying oligonucleotides.
- Limitations in current detection and quantitation methods are identified.
Conclusions:
- There is a significant need for enhanced bioanalytical tools for oligonucleotide analysis.
- Addressing the challenges in oligonucleotide bioanalysis is key to advancing therapeutic applications.
- Future research should focus on developing more sensitive and robust analytical methods.
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