Fecal recovery of dose as parent and metabolites in bile-intact rats and dogs
See Supplemental Figs. 1 and 2 and Supplemental Tables 1 and 2 for a detailed summary of the metabolite identification data.
| Peak | [M+H]+ | Proposed Metabolite | 0–24-Hour Rat Feces (% Dose) | 0–48-Hour Dog Feces (% Dose) |
|---|---|---|---|---|
| P | 513 | LY2090314 | 2.43 | 4.10 |
| M1 | 531 | Parent + O + 2H | 0.62 | 1.15 |
| M4 + M5a | 445 and 624 | Parent − C5H8 | 6.12 | 2.92a |
| M6 | 531 | Parent + O + 2H | NA | |
| M7 | 547 | Parent + O + H2O | 5.14 | |
| M8 + M9a | 547 | Parent + O + H2O | 2.09 | |
| M10 + M53b | 517 and 561 | Parent + 2O − C2H4 and Parent + 3O | 3.53 | 1.87 |
| M11 | 561 | Parent + 3O | 4.19 | 0.69 |
| M13 | 525 | Parent + O − 4H | 3.28 | NA |
| M15 | 527 | Parent + O − 2H | 0.33 | |
| M16 | 529 | Parent + O | 0.49 | |
| M18 | 529 | Parent + O | 0.62 | |
| M22 | 545 | Parent + 2O | 13.14 | 23.08 |
| M23 | 531 | Parent + H2O | 3.65 | 2.92 |
| M24 | 529 | Parent + O | 21.73 | 1.66 |
| M25 | 529 | Parent + O | 0.21 | 0.57 |
| M28 + M42c | 531 | Parent + H2O | 1.15 | 0.73 |
| M31d | 531 | Parent + H2O | 0.00 | NA |
| M32 | 836 | Parent + O + Glutathione | 0.12 | |
| M33 | 529 | Parent + O | 0.69 | 0.32 |
| M34 | 547 | Parent + O + H2O | 2.18 | 5.20 |
| M36 | 529 | Parent + O | 0.29 | NA |
| M39 | 689 | Parent + Glucuronide | NA | 5.42 |
| M40 | 579 | Parent + 3O + H2O | 4.79 | |
| M41 | 531 | Parent + O | 0.30 | |
| M45 | 708 | Maleimide hydrolysis to diacid + Glucuronide | 0.10 | |
| M48 | 721 | Parent + 2O + Glucuronide | 0.62 | |
| M49 | 703 | Parent + O − 2H + Glucuronide | 0.56 | |
| M50 | 545 | Parent + 2O | 0.45 | NA |
| M52 | 547 | Parent + O + H2O | NA | 0.53 |
| M54 | 515 | Parent + 2H | 0.85 | |
| Total identified in feces over time interval (% of dose) | 74.91 | 58.38 | ||
| Amount excreted in feces over time interval (% of dose) | 91.8 | 65.8 | ||
NA, not available.
↵a M4 co-eluted with M5, and M8 co-eluted with M9; M5 was not detected in dog feces.
↵b M10 co-eluted with M53 in dog feces; M53 was not detected in rat feces.
↵c M28 co-eluted with M42 in dog feces; M42 was not detected in rat feces.
↵d M31 was detected in rat feces, but the peak was too small to be accurately integrated.