Table 2.
Results summary (sample - average resolution; average % area count) for different forced degradation conditions for finished product samples 123, 183, 789, and 890.a, b.
| Peak IDc | RRTd | Control (Ambient) | Light | Heat | Acid | Base | Oxidative |
|---|---|---|---|---|---|---|---|
| – | 0.12 | 123– 12.0; 2.9 % 183– 12.4; 2.5 % 789−12.1; 2.5 % 890−12.1; 2.2 % |
123– 10.9; 2.8 % 183– 10.6; 2.3 % 789−10.7; 2.4 % 890−10.7; 2.0 % |
123– 11.0; 2.6 % 183– 11.0; 1.9 % 789−11.0; 2.1 % 890−10.9; 1.8 % |
123−14.3; 2.9 % 183−11.7; 2.5 % 789−14.2; 2.7 % 890−14.2; 2.2 % |
123−15.0; 2.8 % 183−13.6; 2.4 % 789−13.3; 2.6 % 890−14.2; 2.1 % |
123−8.0; 3.3 % 183– 9.5; 3.0 % 789−10.9; 3.9 % 890−11.1; 3.1 % |
| – | 0.15 | NP | NP | NP | NP | NP | NP |
| – | 0.18 | NP | NP | NP | NP | NP | NP |
| – | 0.19 | NP | NP | NP | NP | NP | NP |
| – | 0.23 | NP | NP | NP | NP | 123−15.5; 0.1 %e 183- NP 789- NP 890- NP |
NP |
| – | 0.24 | NP | NP | NP | NP | 123−4.8; 0.1 % 183- NP 789- NP 890−15.5; 0.04 %e |
NP |
| 0.25 | NP | NP | NP | NP | 123−0.7; 0.1 %e 183- NP 789- NP 890- NP |
NP | |
| – | 0.28 | NP | NP | NP | NP | NP | NP |
| – | 0.32 | NP | NP | NP | NP | 123−7.1; 0.1 % 183−21.3; 0.1 % 789−21.8; 0.1 %e 890−18.2; 0.1 % |
NP |
| – | 0.33−0.34 | NP | NP | NP | 123−29.2; 0.1 %e 183– 29.1; 0.1 % 789−29.6; 0.1 %e 890−29.3; 0.1 %e |
123−0.9; 0.6 % 183−0.8; 0.6 % 789−0.8; 0.6 % 890−1.0; 0.5 % |
NP |
| – | 0.37 | NP | NP | NP | NP | NP | NP |
| – | 0.38−0.39 | 123– 25.9; 0.3 % 183– 26.5; 0.2 % 789−26.1; 0.2 % 890−25.8; 0.2 % |
123– 22.8; 0.2 % 183−22.2; 0.2 % 789−22.2; 0.2 % 890−23.0; 0.2 % |
123– 24.4; 0.2 % 183– 23.9; 0.2 % 789−24.1; 0.2 % 890−24.4; 0.2 % |
123−15.3; 0.3 % 183– 5.2; 0.2 % 789−15.1; 0.2 % 890−5.6; 0.2 % |
123−4.5; 0.3 % 183−3.5; 0.2 % 789−3.6; 0.2 % 890−4.9; 0.2 % |
123−22.1; 0.4 % 183– 22.3; 0.4 % 789−22.4; 0.4 % 890−21.9; 0.3 % |
| A – 0.426 (0.417−0.435) | 0.42−0.43 | NP | NP | NP | 123−4.0; 0.1 % 183 – NP 789- NP 890−3.9; 0.1 %e |
123−3.7; 0.1 % 183 – NP 789 – NP 890−3.8; 0.1 % |
NP |
| – | 0.45−0.46 | NP | NP | NP | 123−3.4; 0.2 % 183– 7.7; 0.4 % 789−7.5; 0.4 % 890−6.6; 0.4 % |
123– 2.7; 0.8 % 183– 5.7; 0.8 % 789−5.7; 0.8 % 890−3.0; 0.8 % |
123−4.5; 1.2 % 183– 4.6; 0.7 % 789−4.6; 0.8 % 890−4.5; 0.9 % |
| – | 0.49 | NP | NP | NP | NP | NP | 123−2.4; 0.6 %e 183– 2.4; 0.4 % 789−2.3; 0.5 % 890−2.3; 0.6 %e |
| – | 0.51 | NP | NP | NP | NP | NP | NP |
| – | 0.52 | NP | NP | NP | 123−5.9; 0.2 %e 183– 6.0; 0.2 % 789−5.9; 0.2 %e 890−5.9; 0.2 % |
123−5.2; 0.4 %e 183– 4.3; 0.4 % 789−4.4; 0.4 % 890−5.5; 0.4 % |
123−1.4; 2.6 %e 183– 1.4; 1.6 % 789−1.3; 1.8 % 890−1.3; 2.1 % |
| – | 0.54 | NP | NP | NP | NP | NP | NP |
| – | 0.55−0.56 | NP | NP | NP | NP | NP | 123−1.8; 0.5 % 183– 1.8; 0.4 % 789−1.8; 0.4 % 890−1.8; 0.5 % |
| – | 0.59 | NP | NP | NP | NP | NP | NP |
| I – 0.606 (0.594−0.618) | 0.60 | 123- NP 183- NP 789−14.6; 0.1 % 890- NP |
NP | NP | 123−6.4; 0.1 % 183– 6.0; 0.2 % 789−10.9; 0.2 % 890−6.4; 0.1 % |
123−5.3; 0.4 % 183– 4.4; 0.3 % 789−4.4; 0.4 % 890−5.8; 0.3 % |
123−1.7;0.9 % 183– 2.6; 0.5 % 789−2.6; 0.6 % 890−2.6; 0.7 % |
| – | 0.64 | NP | NP | NP | NP | NP | NP |
| H – 0.709 (0.695−0.723) | 0.71 | NP | NP | NP | NP | NP | NP |
| – | 0.74 | NP | NP | NP | 123 - NP 183– 10.3; 0.1 % 789 - NP 890 - NP |
NP | NP |
| B – 0.796 (0.780 – 0.812) | 0.79−0.81 | NP | NP | NP | 123−14.6; 6.5 % 183– 4.0; 11.2 % 789−14.4; 7.0 % 890−11.5; 10.8 % |
123−12.3; 25.1 % 183– 9.7; 25.3 % 789−9.6; 25.4 % 890−13.7; 24.5 % |
NP |
| – | 0.86 | NP | NP | NP | NP | NP | NP |
| C – 0.887 (0.869 – 0.905) | 0.89 | NP | NP | NP | NP | NP | NP |
| G – 0.924 (0.906−0.942) | 0.91−0.93 | NP | 123– 28.9; 0.6 % 183−28.1; 0.4 % 789−28.7; 0.3 % 890−29.6; 0.3 % |
NP | NP | NP | NP |
| D – 0.958 (0.939 – 0.977) | 0.96 | 123 - NP 183 – 34.4; 0.4 % 789- NP 890−33.8; 0.2 %e |
123 - NP 183– 1.9; 0.4 % 789- NP 890−2.0; 0.3 %e |
123 - NP 183– 32.4; 0.4 % 789- NP 890−34.8; 0.2 % |
123−11.7; 0.3 % 183– 11.8; 0.5 % 789−11.6; 0.5 % 890−11.7; 0.4 % |
123 - NP 183– 8.7; 0.2 % 789- NP 890−11.3; 0.2 % |
123 - NP 183– 15.8; 0.4 % 789- NP 890- NP |
| E – 0.969 (0.950 – 0.988) | 0.97 | NP | NP | NP | NP | NP | NP |
| MPA | 1.00 | 123- 33.6; 96.9 % 183−2.1; 96.9 % 789−20.0; 97.2 % 890−12.3; 97.5 % |
123– 3.5; 96.4 % 183– 1.7; 96.7 % 789−3.4; 97.1 % 890−3.0; 97.4 % |
123−32.5; 97.2 % 183−1.9; 97.6 % 789−31.7; 97.7 % 890−7.3; 97.9 % |
123−2.8; 89.3 % 183– 2.9; 84.7 % 789−2.8; 89.0 % 890−2.8; 85.5 % |
123−12.4; 69.4 % 183– 2.1; 69.6 % 789−10.3; 69.6 % 890−2.8; 70.8 % |
123−15.8; 90.6 % 183– 1.9; 92.6 % 789−16.0; 91.6 % 890−16.6; 91.8 % |
NP – no readily integrable peak.
– Peak purity (PP) data was collected for peaks with large enough area counts, where the average / %RSD for the different samples were obtained as indicated (123–999.9 / 0.01 %; 183–999.9 / 0.01 %; 789–998.2 / 1.25 %; 890–999.8 / 0.1 %).
– Non-degraded (maintained at ambient); light (2.6 × 106 lux hours); heat (14d at 80 °C); acid (7d in 0.2 N HCl); base (4 h in 0.1 N NaOH); oxidative (7d in 3% H2O2 at 37 °C).
– Proposed assignments based on observed relative retention times (RRT) for impurities in Reference solution A injections, including +/- 2% RRT range observed (see Fig. 3). ‘- ‘indicates either degradation product or excipient, where further identifications are proposed in Table 3 in conjunction with MS observations.
– Average relative retention times observed for different forced degradation sample injections.
– Peak was not present in all injects across the various samples.