TABLE 2

Identification of in vivo metabolites of ibrutinib

ComponentIdentityRetention Timem/z (mass/charge ratio)m/z 14CTypical MS FragmentMatrix
M1+138 (JNJ-54243696+O+Gluc)10.21579.2203—a202-320-403-496P
M4+42 (JNJ-54243696+O+SO3)12.81483.1451—a308-320-400-403-404B, P
M7+114 (N-ring opened alcohol+O+SO3)14.24555.1662557.1694156-320-404-457-475U
M10+130 (dihydrodiol+O+SO3)15.75571.1611573.1643154-172-320-403-431-461-473-491U
M11+48 (N-ring opened acid+O)15.83489.1886491.1918152-170-320-417-471F, B, P
M17+34 (N-ring opened alcohol+O)17.64475.2094477.2126138-156-320-404F, U
M20+48 (N-ring opened acid+O)19.39489.1886491.1918400-418F, U, B, P
M21+96 (+O+SO3)19.57537.1556539.158884-138-320-403-457U, B, P
M23−54 (JNJ-54243696)20.10387.1933—a84-181-209-287-304F, B, P
M24+52 (N-ring opened alcohol+2O+2H)20.32493.2199495.2231172-190-304-405-475F, U, B, P
M25+32 (N-ring opened acid)20.89473.1937475.1969152-170-304-342-401-455F, U, B, P
M29+34 (N-ring opened alcohol+O)22.37475.2094477.2126156-304-320-386-404F, U, B, P
M30(JNJ-54243696+O-2H)22.79401.1726—a181-210-287-304F, B, P
M31+178 (+2H+CGSC)23.10619.2451621.2549304-387-441-473-601B, P
M32+163 (+2H+MASC)23.71604.2342606.2374304-387-441-473-562F, U
M33+161 (+MASC)24.11602.2186604.2218304-385-439-473F
M34+18 (N-ring opened alcohol)23.63459.2145461.217784-102-138-156-304-321-388-441F, U, B, P
M35+16 (+O)23.77457.1988459.202084-138-304-320-374-403F, B
M36+18 (+O+2H)24.59459.2145461.217784-140+320+403F
M37+34 (dihydrodiol)25.41475.2094477.212684-154-172-304-387-445-457F, U, B, P
M39+16 (+O)28.06457.1988459.2020304-385-439B, P
M40+16 (+O)28.75457.1988459.2020304-385-439B, P
UDUnchanged Drug30.20441.2039443.2071304-385-439F, B, P

  • B, blood; CGSC, cysteine-glycine conjugate; F, feces; Gluc, glucuronide; MASC, mercapturic acid conjugate; P, plasma; SO3, sulfate conjugate; U, urine.

    a: not applicable as the metabolite does no longer contain the 14C-label.