Stability study of selected adenosine nucleosides using LC and LC/MS analyses

Area of Science:

• Chemical Stability
• Nucleoside Chemistry
• Analytical Chemistry

Background:

• Adenosine is a naturally occurring nucleoside with vital biological roles.
• Synthetic nucleoside analogs are crucial for drug development and biochemical research.
• Understanding nucleoside stability is essential for their application and storage.

Purpose of the Study:

• To assess the chemical stability of adenosine and two chlorinated analogs.
• To determine the impact of chlorine substitution on nucleoside hydrolysis.
• To identify hydrolysis products and kinetics under varying conditions.

Main Methods:

• High-performance liquid chromatography (LC) for stability measurements.
• Liquid chromatography-mass spectrometry (LC/MS) for hydrolysis product identification.
• Kinetic analysis of hydrolysis rates and half-lives across a pH range (2-10) and temperatures (40-80°C).

Main Results:

• Nucleoside hydrolysis followed pseudo-first order kinetics.
• LC/MS identified adenine (m/z 136.3) and 2-chloroadenine (m/z 170.3) as hydrolysis products.
• 2-chloroadenosine exhibited increased stability against acid hydrolysis compared to adenosine and 5'-chloro-5'-deoxyadenosine.

Conclusions:

• Chlorine substitution in the nucleoside base moiety enhances stability.
• The findings provide insights into the degradation pathways of nucleoside analogs.
• This research aids in the rational design and application of stable nucleoside derivatives.