TABLE 5

Acalabrutinib metabolites identified in human plasma, urine, and feces

ComponentProposed IdentificationRetention Time m/zExcreted DoseAUC
Human Plasma
Human FecesHuman Urine
min%
M2Oxidation, amide hydrolysis11.3a406.1506TraceTraceND
M3Oxidation, dealkylation17.2a431.14591.81.32.5
M37[M + H]+ = 44222.1a442.1983TraceTraceND
M5 (ACP-5530)GSH adduct24.3b773.2808NDND2.2
M7 (ACP-5531)Cysteinylglycine adduct27.6b644.2381ND2.710.8
M9Oxidized ACP-553127.7b660.2328ND
M10 (ACP-5461)Cysteine adduct28.1b587.2178Trace
M11Oxidized ACP-546128.3a603.2129Trace
M14 (ACP-5825)Oxidation (pyrrolidine)29.5a482.1928TraceTraceND
M16Reduction of M2730.9a484.20882.90.62.2
M17Reduced ACP-5134, pyrrolidine oxidation, and dehydration31.6a484.20875.2TraceND
M18Two oxidations (+O2)31.4c498.1879NDTrace
M22Two oxidations (+O2)33.0a498.187812.10.5Trace
M45Reduced ACP-513433.0c486.2242TraceTrace
M23 (ACP-5134)Hydrated alkyne33.6a484.2086TraceTrace
M24Reduced ACP-5134 +O34.2a502.21927.5TraceTrace
M25Oxidation (pyrrolidine), dehydration35.6a464.1825Trace0.25.9
ParentAcalabrutinib38.5b466.19831.20.58.6
M27 (ACP-5862)Oxidation (pyrrolidine), ring opening41.6b482.19353.50.534.7
  • 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.