Stability-Indicating Gradient RP-LC Method for the Determination of Process and Degradation Impurities in Bosentan Monohydrate: An Endothelin Receptor Antagonist
Table 2
Forced degradation study results.
Stress condition
% Assay of bosentan
% of degradant
Observation and mass balance
Peak purity
PA
PT
Undegraded
99.95
—
0.180
0.375
Acid hydrolysis (Conc. HCl, 4 h refluxed)
85.84
13.14
Increase in levels of Imp-B (3.28%) and Imp-E (0.41%) and other 9.44% of unknown degradation product formed. (Mass balance: 99.0%)
0.178
0.303
Base hydrolysis (5 M NaOH, 48 h refluxed)
87.32
14.25
Increase in levels of Imp-A (0.47%) and major degradation product i.e. Imp-B (13.78%) formed. (Mass balance: 101.6%)
0.178
0.317
Oxidation (6% H2O2 at RT)
98.80
ND
No any known and unknown degradation product formed. (Mass balance: 99.0%)
0.178
0.367
Thermal (60°C, 8-days)
100.31
ND
No any known and unknown degradation product formed. (Mass balance: 100.3%)
0.184
0.377
Photolytic as per ICH
99.16
ND
No any known and unknown degradation product formed. (Mass balance: 99.2%)
0.179
0.368
Mass balance = % assay + % sum of all impurities + % sum of all degradants; PA: purity angle; PT: Purity threshold; ND: not detected.
