TABLE 4

Relevant metabolites of [14C]casopitant in human plasma, urine, and feces after a single-dose i.v. (90 mg, 35 μCi) and oral (150 mg, 75 μCi) administration of [14C]casopitant

The underlined metabolites in the table have been confirmed with either NMR or comparison with standard.

Matrix
Proposed Structure
Positive [M + H]+ or Negative [M + H]-Ion MS Products Ions (m/z)
1H-NMR (600Mhz, 1:1 ACN:D2O) (Where Available)
PL, FE Embedded Image Casopitant 617 [M + H]+ 7.89 (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 vs. broad.
489, 481, 346, 327, 298, 277, 241, 210, 167
PL Embedded Image M2 649 [M + H]+ 7.90 (brs, 1H), 7.60 (brs, 2H), 7.25 (m, 1H), 7.07 (dd, 1H) 6.83 (m, 1H), 5.78 and 5.38 (m, 1H, rotamers, CHOH) 5.35 (q, 1H), 4.75 and 4.65 (d, 1H each, CH2OH), 3.44 (m, 1H), 2.81 (m, 1H), 2.65 (s, 3H), 1.46 (d, 3H), several signals broad and/or obscured.
631, 479, 291, 245, 241, 208, 183, 173, 165
PL, FE Embedded Image M3 633 [M + H]+ 7.90 (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.
615, 505, 481, 369, 362, 241, 210, 173, 167
PL, FE Embedded Image M10 619 [M + H]+
489, 327, 298, 241, 175
PL Embedded Image GSK631832 (M12) 589 [M + H]+
489, 453, 249, 241, 182, 139
PL Embedded Image GW525060 (M13) 633 [M + H]+ 7.88 (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.
615, 497, 489, 479, 461, 275, 183, 165
UR Embedded Image M21 393 [M + H]+ 7.20 (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.
MS/MS of [M + H]+ - H2O: 344, 275, 239, 208, 165
UR Embedded Image M28 377 [M + H]+ 7.21 (dd, 1H), 6.92-6.97 (m, 2H), 2.49 (s, 3H), 2.34 (s, 3H) several signals broad and/or obscured.
241, 210, 167
PL, FE Embedded Image GSK517142 (M31) 591 [M + H]+
489, 455, 327, 320, 251, 241, 184, 175, 141
PL, FE Embedded Image M39 523 [M + H]+ 7.89 (brs 1H), 7.75 (brs, 2H), 7.20 (dd, 1H), 6.89-6.83 (m, 2H), 2.62 (s, 3H), several signals broad and/or obscured.
315, 241, 209, 208, 191, 149
PL, UR Embedded Image GSK1735004 (M44) 433 [M-H]- 7.91 (brs, 2H), 8.03 (brs, 1H), 5.18 (q, 1H) 4.09 (d, 1H, anomeric) 1.45 (d, 3H)
415, 241, 213, 175
FE Embedded Image M50 647 [M + H]+
332, 272, 241, 210, 204, 167
FE Embedded Image M63 633 [M + H]+
467, 350, 332, 290, 222, 210, 204, 167
FE Embedded Image M73 651 [M + H]+
633, 505, 499, 380, 369, 327, 298, 241, 228, 185
PL, FE Embedded Image M77 607 [M + H]+
589, 455, 336, 241, 190, 184, 173, 141
FE Embedded Image M80 663 [M + H]+
645, 330, 305, 241, 208, 204
FE Embedded Image M123 564 [M + H]+
489, 428, 327, 315, 298, 272, 241, 224, 175, 157, 114
PL, FE Embedded Image GSK2110277 (M134) 506 [M + H]+
370, 315, 298, 241, 175
FE Embedded Image M137 619 [M + H]+ 7.91 (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.
304, 286, 276, 272, 241, 204, 182
UR Embedded Image M138 393 [M + H]+
MS/MS of [M + H]+ - H2O ion: 344, 275, 239, 208, 165
UR Embedded Image M139 393 [M + H]+
MS/MS of [M + H]+ - H2O ion: 275, 239, 208, 165
FE Embedded Image M140 665 [M + H]+
No MS/MS data
FE Embedded Image M141 621 [M + H]+
350, 306, 290, 241, 184, 141
FE Embedded Image M146 580 [M + H]+
562, 241, 173, 157, 114
PL Embedded Image M156 567 [M-H]-
314, 296, 253, 208
PL, FE
Embedded Image M157
553 [M-H]- 7.90 (brs, 1H), 7.61 (brs, 2H), 7.24 (dd, 1H), 7.07 (dd, 1H) 6.84 (dt, 1H), 4.74 and 4.65 (d, 1H each, CH2OH), 2.65 (s, 3H), several signals broad and/or obscured.
314, 282, 270, 213, 194, 163

  • PL, plasma; UR, urine; FE, feces.