Component | Proposed Identification | Retention Time | m/z | Excreted Dose | AUC Human Plasma | |
---|---|---|---|---|---|---|
Human Feces | Human Urine | |||||
min | % | |||||
M2 | Oxidation, amide hydrolysis | 11.3a | 406.1506 | Trace | Trace | ND |
M3 | Oxidation, dealkylation | 17.2a | 431.1459 | 1.8 | 1.3 | 2.5 |
M37 | [M + H]+ = 442 | 22.1a | 442.1983 | Trace | Trace | ND |
M5 (ACP-5530) | GSH adduct | 24.3b | 773.2808 | ND | ND | 2.2 |
M7 (ACP-5531) | Cysteinylglycine adduct | 27.6b | 644.2381 | ND | 2.7 | 10.8 |
M9 | Oxidized ACP-5531 | 27.7b | 660.2328 | ND | ||
M10 (ACP-5461) | Cysteine adduct | 28.1b | 587.2178 | Trace | ||
M11 | Oxidized ACP-5461 | 28.3a | 603.2129 | Trace | ||
M14 (ACP-5825) | Oxidation (pyrrolidine) | 29.5a | 482.1928 | Trace | Trace | ND |
M16 | Reduction of M27 | 30.9a | 484.2088 | 2.9 | 0.6 | 2.2 |
M17 | Reduced ACP-5134, pyrrolidine oxidation, and dehydration | 31.6a | 484.2087 | 5.2 | Trace | ND |
M18 | Two oxidations (+O2) | 31.4c | 498.1879 | ND | Trace | |
M22 | Two oxidations (+O2) | 33.0a | 498.1878 | 12.1 | 0.5 | Trace |
M45 | Reduced ACP-5134 | 33.0c | 486.2242 | Trace | Trace | |
M23 (ACP-5134) | Hydrated alkyne | 33.6a | 484.2086 | Trace | Trace | |
M24 | Reduced ACP-5134 +O | 34.2a | 502.2192 | 7.5 | Trace | Trace |
M25 | Oxidation (pyrrolidine), dehydration | 35.6a | 464.1825 | Trace | 0.2 | 5.9 |
Parent | Acalabrutinib | 38.5b | 466.1983 | 1.2 | 0.5 | 8.6 |
M27 (ACP-5862) | Oxidation (pyrrolidine), ring opening | 41.6b | 482.1935 | 3.5 | 0.5 | 34.7 |
Grouped metabolites coeluted in the same fractions comprising the reconstructed chromatographic trace. Trace indicates that the component was observed via MS/MS, but 14C was not above baseline. m/z, mass-to-charge ratio; ND, not detected.
↵a Retention time from human urine chromatograms.
↵b Retention time from human plasma chromatograms.
↵c Retention times from human feces chromatograms.