Structure Elucidation and In-Silico Safety Assessment of a Degradation Impurity in Molnupiravir Capsule Formulation: Development of a Stability-Indicating Method for Related Substances
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View abstract on PubMed
Summary
This summary is machine-generated.A new RP-HPLC method accurately quantifies molnupiravir impurities in COVID-19 treatments. An identified N-hydroxycytidine impurity shows potential toxicity, necessitating further safety studies for quality control.
Area Of Science
- Pharmaceutical Analysis
- Drug Quality Control
- Antiviral Drug Development
Background
- Molnupiravir is an FDA-approved antiviral for COVID-19 treatment.
- Reliable analytical methods are crucial for ensuring molnupiravir's quality and safety.
- Therapeutic importance necessitates rigorous quality assurance.
Purpose Of The Study
- Develop a stability-indicating RP-HPLC method for molnupiravir impurities.
- Identify and elucidate the structure of an unknown impurity.
- Assess the potential safety profile of the identified impurity.
Main Methods
- Developed and validated a stability-indicating RP-HPLC method.
- Utilized LC-TQ/MS and NMR spectroscopy for structural elucidation.
- Employed admetSAR tool for in-silico safety assessment.
Main Results
- The RP-HPLC method showed excellent linearity (R2 ≥ 0.9990) and precision (RSD < 1.34%).
- Sensitivity was high with LOD of 0.2 µg/mL and LOQ of 0.4 µg/mL.
- An unknown impurity was identified as N-hydroxycytidine and predicted to have potential hepatotoxicity, mitochondrial toxicity, and reproductive toxicity.
Conclusions
- The validated RP-HPLC method effectively quantifies molnupiravir impurities for quality control.
- The identified N-hydroxycytidine impurity requires further in vivo safety evaluation.
- This research enhances the quality control of molnupiravir for COVID-19 treatment.
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