TABLE 2

Relevant metabolites of [14C]casopitant

Underlined metabolites have been confirmed with either NMR or comparison with standards.

Proposed StructurePositive [M + H]+ or Negative [M + H] Ion MS Products Ions (m/z)1H NMR (600 MHz, 1:1 ACN-D2O (Where Available)
Embedded Image Casopitant617 [M + H]+ 489, 481, 346, 327, 298, 277, 241, 210, 1677.89 (brs, 1H), 7.59 (brs, 2H), 7.21 (dd, 1H), 6.88 (dd, 1H) 6.76 (dt, 1H), 5.32 (q, 1H, NCHCH3), 4.23 (m, 1H), 3.49 (m, 1H), 2.86 (m, 1H), 2.69 (s, 3H, NCH3), 2.34 (s, 3H), 1.46 (d, 3H, CHCH3), several piperidine and piperazine signals versus broad
Embedded Image M1619 [M + H]+ 601, 467, 318, 190, 167, 336, 208
Embedded Image M3633 [M + H]+ 615, 505, 481, 369, 362, 241, 210, 173, 1677.90 (brs, 1H), 7.60 (brs, 2H), 7.25 (dd, 1H), 7.07 (dd, 1H) 6.84 (dt, 1H), 5.35 (q, 1H), 4.74 and 4.64 (d, 1H each, CH2OH), 2.65 (s, 3H), 1.46 (d, 3H), several signals broad and/or obscured
Embedded Image M9603 [M + H]+ 489, 327, 298, 241, 175
Embedded Image M10619 [M + H]+ 489, 327, 298, 241, 175
Embedded Image GSK631832589 [M + H]+ 489, 453, 249, 241, 182, 139
Embedded Image GW525060633 [M + H]+ 615, 497, 489, 479, 461, 275, 183, 1657.88 (brs, 1H), 7.59 (brs, 2H), 7.16 (m, 1H), 6.84 (dd, 1H) 6.72 (m, 1H), 5.81 and obscured (m, 1H, rotamers, CHOH) 5.35, several signals broad and/or obscured
Embedded Image M16393 [M + H]+ 336, 210, 208, 190, 167
Embedded Image M17391 [M + H]]+ 210, 190, 167
Embedded Image M21393 [M + H]]+ MS/MS of [M + H]]+-H2O: 344, 275, 239, 208, 1657.20 (dd, 1H), 6.92–6.98 (m, 2H), 5.74 and 5.39 (m, 1H, rotamers, CHOH), 2.49 (s, 3H), 2.34 (s, 3H) several signals broad and/or obscured
Embedded Image M22391 [M + H]]+ 192, 184, 167
Embedded Image M28377 [M + H]]+ 241, 210, 1677.21 (dd, 1H), 6.92–6.97 (m, 2H), 2.49 (s, 3H), 2.34 (s, 3H) several signals broad and/or obscured
Embedded Image GSK517142 (M31)591 [M + H]]+ 489, 455, 327, 320, 251, 241, 184, 175, 141
Embedded Image M33635 [M + H]]+ 617, 465, 291, 245, 208, 165, 180
Embedded Image M37647 [M + H]]+ 489, 467, 327, 298, 263, 241, 197, 153
Embedded Image M41635 [M + H]]+ 617, 505, 487, 336, 327, 298, 272, 241, 190, 173, 131
Embedded Image GSK1735004 (M44)433 [M-H] 415, 241, 213, 1757.91 (brs, 2H), 8.03 (brs, 1H), 5.18 (q, 1H), 4.09 (d, 1H, anomeric), 1.45 (d, 3H)
Embedded Image M50647 [M + H]]+ 332, 272, 241, 210, 204, 167
Embedded Image M57607 [M + H]]+ 548, 489, 412, 327, 298, 241, 141
Embedded Image M61649 [M + H]]+ 631, 465, 348, 330, 305, 222, 208, 165
Embedded Image M63633 [M + H]]+ 467, 350, 332, 290, 222, 210, 204, 167
Embedded Image M69603 [M + H]]+ 475, 467, 346, 277, 241, 210, 167
Embedded Image M70591 [M + H]]+ 573, 308, 290, 208, 190, 182
Embedded Image M78699 [M + H]+ 523, 505, 487, 371, 327, 298, 241
Embedded Image M80663 [M + H]+ 645, 330, 305, 241, 208, 204
Embedded Image M81, M82896 [M + H]+ 767, 589, 571, 489, 453, 446, 308
Embedded Image M100, M102, M106, M118823 [M + H]+ 805 (not for M118), 647, 519 (M100 only), 481 (not for M118), 332, 290 (not for M118), 272 (M100 only), 241(not for M118), 210, 204(not for M118), 167(not for M118)
Embedded Image M103809 [M + H]]+ 633, 615, 505, 481, 362, 210, 167
Embedded Image M104683 [M + H]]+ 507, 489, 397, 379, 327, 298, 241, 175
Embedded Image M109633 [M + H]]+ 489, 392, 327, 298, 241, 163
Embedded Image M114287 [M-H] 269, 243, 223, 203, 195
Embedded Image M115257 [M-H] 213, 193, 173
Embedded Image M117337 [M-H] 257, 237, 213, 97
Embedded Image M119825 [M + H]]+ 807, 649, 631, 613, 505, 479, 467, 291, 245, 226, 208, 183, 165
Embedded Image or Embedded Image M120797 [M + H]]+ 621, 184
Unknown cysteine conjugate M122738 [M + H]]+ 672, 489, 401, 327, 241, 184
Embedded Image M123564 [M + H]]+ 489, 428, 327, 315, 298, 272, 241, 224, 175, 157, 114
Embedded Image GSK2110277 (M134)506 [M + H]]+ 370, 315, 298, 241, 175
Embedded Image M136449 [M-H] 273, 255, 243, 213, 193, 113a: 7.92 b: 8.00 c: 5.04 d: 3.80,3.91 Gluc. anomeric: 4.45
Embedded Image M137619 [M + H]]+ 304, 286, 276, 272, 241, 204, 1827.91 (brs, 1H), 7.61 (brs, 2H), 7.26 (dd, 1H), 7.07 (dd, 1H) 6.84 (dt, 1H), 5.35 (q, 1H), 4.74 and 4.66 (d, 1H each, CH2OH), 2.62 (s, 3H), several signals broad and/or obscured
Embedded Image M138393 [M + H]]+ MS/MS of [M + H]]+-H2O ion: 344, 275, 239, 208, 165
Embedded Image M141621 [M + H]]+ 519, 455, 350, 306, 290, 241, 204, 184, 141
Embedded Image or Embedded Image M155607 [M + H]]+ 489, 241, 200, 157
Embedded Image M169550 [M + H]]+ 414, 327, 298, 279, 272, 241, 210, 184, 175, 143, 100
Embedded Image M171, M172, M173839 [M + H]]+ 821, 803 (not for M171), 663 (M171 only), 645 (M171 only), 479 (M173 only), 330 (not for M172), 305(M171 only), 272(M171 only), 208, 165 (M173 only)
  • ACN, acetonitrile; D2O, deuterium oxide.