Table 4. Control Strategy and Impurity Limit of Process-Related Impurity.
| intermediate | crude product | control strategya | retention time (min) | impurity limit |
|---|---|---|---|---|
| 4 | recrystallized twice, first in MeOH and then in ethyl acetate: | 12.563 | ||
| Imp-1 (ND)b | 12.125 | Imp-1 <0.10% | ||
| Imp-2 (ND)b | Imp-3 (1.35%) | 11.993 | Imp-2 <0.10% | |
| Imp-3 (2.6%)a | 13.402 | Imp-3 <1.5% | ||
| 5 | recrystallized with ethyl acetate: 4 (0.07%) | 10.825 | ||
| 4 (0.2%)a | 12.563 | 4 <0.10% | ||
| Imp-3 (0.6%) | 13.402 | Imp-3 <0.10% | ||
| Imp-4 (ND)b | 10.476 | Imp-4 <0.10% | ||
| Imp-5 (0.5%)a | 11.277 | Imp-5 <0.10% | ||
| Imp-6 (ND)b | 10.244 | Imp-6 <0.10% | ||
| 6 (LCA) | recrystallized with MeOH/DCM (10:1): | 8.658 | ||
| Imp-7 (ND)b | 6.787 | Imp-7<0.10% | ||
| Imp-8 (ND)b | 6.524 | Imp-8 <0.10% | ||
| Imp-9 (ND)b | Imp-10 (0.07%) | 9.216 | Imp-9 <0.10% | |
| Imp-10 (0.08%)a | 9.352 | Imp-10 <0.10% | ||
| Imp-11 (ND)b | 8.936 | Imp-11 <0.10% |
a
Content assay of impurities in product using the peak area normalization method.
b
Not detected on HPLC.