Identification, Separation and Characterization of Acidic and Oxide Degradation of Atazanavir Sulphate Under ICH-Recommended Stress Conditions by HPTLC with MS/ TOF

Background

Studies have indicated that atazanavir is prone to degradation in environments with high levels of acidity and oxidative stress. However, the drug demonstrated stability when exposed to basic, neutral, photolytic and thermal stresses. There were two Degradation Products (DPs) from the stress studies.

Materials and Methods

An assessment of Atazanavir sulphate (ATV) stability under various stress conditions were carried out using the International Conference on Harmonisation (ICH) Q1A (R2) recommendations as a foundation for work. Pre-treated silica gel 60F254 plates were combined with ethyl acetate: methanol (9:1 (v/v)) mobile phase to create a chromatographic profile.

Results

An approach that combines high-resolution Mass Spectrometry (MS/TOF) with Infrared (IR) spectroscopy was used on a variety of stress-exposed substances to clarify functional moieties and extract mass spectral data. First, a thorough fragmentation pathway for the parent medication was mapped using the high-resolution mass spectral data, which was then applied to its degradation products. Each fragment was given a structural suggestion based on the most likely molecular formulas.

Conclusion

Based on this investigation, two new degradation products were found: methyl N-[(1S) -1-{[(2S,3S) -3-hydroxy -4-[(2S)-2-[(methoxycarbonyl)amino] -3,3-dimethylbutanehydrazido] -1 -phenylbutan-2-yl] carbamoyl} -2,2-dimethylpropyl] carbamate and (2S,3S)-3-amino -4-phenyl-(1-(4-(pyridine-2-yl) benzyl)hydrazinyl)butan-2-ol.