TABLE 3

Identification of in vivo metabolites of apalutamide after a single oral dose of 240 mg in healthy men

ComponentIdentityRetention Time LC-AMS (min) UrineRetention Time LC-AMS (min) FecesRetention Time LC-MS (min)m/zTypical MS FragmentsMatrix
M2−16 (−S+O)18.7–18.923.0462.1189162, 193, 214, 403, 434U
M3−14 (N-demethylation)19.7–19.918.7–18.924.1464.0804162, 179, 190, 207, 419, 436, 447F, U, P
M4−13 (oxidative deamination)16.3–16.915.721.1465.0644162, 180, 208, 230, 437F, U, P
M8+16 (+O)17.3–17.516.321.7494.091162, 193, 206, 211, 219, 230, 381, 419, 450F, U
M9+104 (cysteine condensation)13.3–13.512.517.7582.0893105, 249, 334, 478, 508F, U
M10+161 (cysteine-glycine condensation)17.9639.1107116, 162, 249, 391, 478, 508, 536U
M11+192 (+O+gluc)12.9–13.117.4670.1231162, 193, 219, 381, 419, 450, 494U
M12+147 (cysteine-glycine addition+N- demethylation)12.316.8625.0951116, 162, 235U
M13+18 (water addition)12.311.316.5496.1066231, 248, 249, 479F, U
M14+90 (cysteine addition+N-demethylation)12.111.316.5568.0736105, 235, 334F, U
M15+4 (water addition+N-demethylation)10.915.1482.091218, 235, 248, 249, 409, 454, 465F, U
M17+91 (cysteine addition+oxidative  deamination)14.6569.0576105, 208, 236, 334F, U
M18+5 (water addition+oxidative  deamination)8.37.512.7483.075236, 466F, U
M19−211 (ring opening+hydrolysis)5.54.79.7267.114558, 99, 138, 162, 190, 193, 208, 236, 239F, U
M20−225 (ring opening+hydrolysis+ demethylation)4.74.1–4.38.9253.0988138, 162, 179, 190, 208, 225F, U
M21−35 (ring opening+hydrolysis+gluc)3.1–4.18.4443.1466162, 208, 221, 236, 239, 267U
M22−49 (ring opening+hydrolysis+ demethylation+gluc)3.1–4.18.1429.1309162, 208, 225, 236, 253U
UDParent20.7–20.919.7–19.925.1478.0961162, 164, 190, 193, 221, 230, 419, 447, 450F, U, P
  • UD, unchanged drug.