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.

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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