Table 5.
Comparison of toxicities of Cefazolin impurities in zebrafish larvae testing.
| Compounds | LD10 (mmol/L) | LD50 (mmol/L) | Test concentrations (mmol/L) | Concentrations in vivo* (mmol/L) (RSD) | Body burden (mmol/larva‡) | |
|---|---|---|---|---|---|---|
| Cefazolin | 0.18 | 0.26 | 0.11 | 1.5 × 10−5 (10.0) | 5.1 × 10−11 | |
| 0.26 | 2.1 × 10−5 (12.1) | 6.8 × 10−11 | ||||
| First group of impurities | Impurity A | 1.95 | 3.85 | 0.04 | 7.3 × 10−4 (10.0) | 2.4 × 10−9 |
| 3.85 | 0.14 (8.4) | 4.7 × 10−7 | ||||
| Impurity F | 0.07 | 0.11 | 0.04 | 7.6 × 10−3 (3.5) | 2.5 × 10−8 | |
| 0.11 | 3.3 × 10−2 (1.4) | 1.1 × 10−7 | ||||
| Impurity G | 0.88 | 1.32 | 0.18 | 2.2 × 10−5 (4.0) | 7.2 × 10−11 | |
| 0.74 | 3.1 × 10−5 (2.7) | 1.0 × 10−10 | ||||
| Second group of impurities | Impurity H | 0.04 | 0.22 | 0.11 | 8.7 × 10−5 (12.0) | 2.9 × 10−10 |
| 0.22 | 1.4 × 10−4 (20.0) | 4.5 × 10−10 | ||||
| Impurity I | 0.06 | 0.08 | 0.08 | / | 1.5 × 10−10 | |
| Impurity J | ~0.05 | / | 0.31 | 4.5 × 10−5 (8.2) | 2.0 × 10−10 | |
| 0.52 | 6.0 × 10−5 (7.5) | 4.8 × 10−10 | ||||
| Third group of impurities | Impurity K | 0.19 | 0.37 | 0.15 | 1.4 × 10−4 (5.3) | 1.2 × 10−8 |
| 0.37 | 3.6 × 10−3 (6.1) | 2.9 × 10−10 | ||||
| Impurity M | 0.06 | 0.12 | 0.07 | 2.5 × 10−4 (7.5) | 8.4 × 10−10 | |
| 0.12 | 6.4 × 10−4 (5.6) | 2.1 × 10−9 | ||||
| Impurity N | 0.03 | 0.12 | 0.07 | 9.2 × 10−4 (8.3) | 3.1 × 10−9 | |
| 0.12 | 2.1 × 10−3 (11.6) | 6.7 × 10−9 | ||||
/, LD50 was not observed, or impurity in vivo was not determined.
*
50% of the embryos had toxic reactions (teratogenic + lethal);
‡
mmol/larva = concentration(mmol/L) × 100 μL/30 (zebrafish number) × 10−6.