RESUMO
Since the stability of the pharmaceuticals plays a crucial role in efficacy and safety while using them in the treatment of disorders, the evaluation of purity and impurity profiling of pharmaceuticals is of utmost importance using efficient analytical techniques. The present study explains the identification, isolation, and characterization of stress degradation products of the anti-human immunovirus drug Darunavir. The degradation study was performed to evaluate the stability profile of Darunavir in different stress conditions like hydrolytic, oxidative, thermal, and photolytic conditions as per the ICH guidelines. Degradation products were identified using ultra-performance liquid chromatography coupled with mass spectrometry, isolated using semi-preparative high-performance liquid chromatography, and structural characterization by HRMS and 1H, 13C NMR (1D, 2D). Darunavir is relatively stable in oxidative, thermal, and photolytic conditions; however, considerable degradation was observed in acid and base hydrolysis. A total of five degradation products were identified and isolated in acid and base degradation. DP-1, DP -2, & DP-3 were observed in acid conditions, whereas in base conditions, along with DP-2, two more DPs, i.e., DP-4 & DP-5, were identified. Among the five DPs, two degradation products, namely DP-1: N-(4-(N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylsulfamoyl) phenyl) acetimidamide. & DP-3: hexahydrofuro[2,3-b]furan-3-yl(4-((4-acetimidamido-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate, are novel, remaining degradation products DP-2: 4-amino-N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide, DP-4: 4-amino-N-(((5S)-4-benzyl-2-oxooxazolidin-5-yl) methyl) -N-isobutyl benzenesulfonamide and DP-5: methyl ((3S)-4-((4-amino-N-isobutylphenyl) sulfonamido)-3-hydroxy-1-phenylbutan-2-yl) carbamate are already reported tentatively using a single analytical technique coupled with mass analysis without any evidence from NMR and IR data. Hence, the present study focused on using High-Resolution Mass, 1D, and 2D 1H, 13C NMR data for concrete confirmation of structures for degradation products. Supplementary Information: The online version contains supplementary material available at 10.1007/s10337-022-04226-z.
RESUMO
The current research explains the stress degradation behavior of Apixaban, which is an anticoagulant or blood thinner. The degradation was conducted using hydrolytic, oxidative, thermal, and photolytic conditions. Apixaban is relatively stable in oxidative, thermal, and photolytic conditions; however, considerable degradation was observed in acid and base hydrolysis. Degradation products were identified using ultra-high performance liquid chromatography-mass spectrometry, isolated using semi-preparative high-performance liquid chromatography, and structural characterization by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. A total of five degradation products were identified and isolated in acid and base degradation. Degradation products 1, 2, and 3 were observed in acid conditions, whereas in base conditions, along with those three, two more degradation products 4 and 5 were identified. The representative thing was that among the five degradation products, two sets of positional isomers 1, 4, and 2, 5 were observed; out of which 2 and 5 are novel. The remaining degradation products 1, 3, and 4 are already reported tentatively using a single analytical technique of mass analysis without any evidence from nuclear magnetic resonance spectroscopy. Hence, the present study focused on using high-resolution mass, and nuclear magnetic resonance spectroscopy data for concrete confirmation of structures for degradation products.
