Identification, isolation, and structural characterization of novel forced degradation products of apixaban using advanced analytical techniques

Abstract

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 chromatographymass 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.

Stability‐indicating method for quantification of potential genotoxic impurity and other organic impurities of chlorzoxazone using hyphenated techniques

“…According to ICH, forced degradation experiments were conducted using chlorzoxazone active pharmaceutical ingredient (API), drug product, and placebo at test concentrations of 2.5 mg/mL to evaluate the degradation behavior of chlorzoxazone and respective excipients as well as the stability‐indicating capabilities of the developed method [31–34]. The degradation study was conducted under different conditions, like photolytic (exposure light: 1.2 million lux‐hours and UV: 200 W‐h/m 2 ), thermal (at 105°C for 12 h), acidic (5 N HCl for 120 min at 60°C), alkaline (5 N NaOH for 120 min at 60°C), oxidation (30% of peroxide solution for 120 min at 60°C) and humidity (90% relative humidity, 25°C for 7 days).…”

“…According to ICH, forced degradation experiments were conducted using chlorzoxazone active pharmaceutical ingredient (API), drug product, and placebo at test concentrations of 2.5 mg/mL to evaluate the degradation behavior of chlorzoxazone and respective excipients as well as the stability-indicating capabilities of the developed method [31][32][33][34]. The degradation study was conducted under different conditions, like photolytic (exposure light:…”

Identification, Isolation, and Structural Characterization of Novel Forced Degradation Products of Darunavir Using Advanced Analytical Techniques Like UPLC–MS, Prep-HPLC, HRMS, NMR, and FT-IR Spectroscopy

“…As a result, ~ 15–20% of degradation was observed in both acid (1 N HCl with stirring at room temperature, up to 48 h) and base (1 N NaOH with stirring at room temperature, up to 36 h) conditions. Detailed degradation conditions [ 16 – 21 ] and results are displayed in Table 1 , and degradation chromatograms of acid and base hydrolysis are shown in Fig. 2 .…”

Isolation and identification of forced degradation products of Febuxostat

“…Few works of literature are available for the analysis of Febuxostat. Recently, several pseudo-DPs were captured in a journal where acetonitrile and methanol were used as co-solvents and reacted with the drug during forced degradation [13][14][15][16][17][18][19][20][21][22]. Hence, the current study aimed to identify novel acid DPs with advanced techniques (2D NMR and high-resolution MS [HRMS]).…”