Identity of various metabolites of RWJ-333369 in mice (M), rats (R), rabbits (Rb), and dogs (D) after single oral administration of 14C-RWJ-333369
Identity of M2 (rat), M3 (dog), M7 (mouse, rat, dog and rabbit), M15 (mouse, rat), M17 (dog) is unknown.
Metabolite No. | Species | Identification Method | Identity | MH+ or M- or MA | Typical MS or MS2/3 Fragments |
|---|---|---|---|---|---|
| UD | M, R, Rb, D | Cochromatography, LC-MS/MS | RWJ-333369, UD | 216, 232, 238 | 119, 137, 155, 198 |
| M1 * | M, R, Rb, D | Cochromatography, LC-MS/MS | R342141, 2-chlorophenylglycine | 186 | 140, 169 |
| M4 * | M, R, Rb | Cochromatography, LC-MS/MS | R300100, 2-chlorobenzoic acid | 155 | 111 |
| M5 * | M, R, Rb, D | Cochromatography, LC-MS/MS | R288222, 2-chloromandelic acid CMA) | 185 | 141, 123, 111 |
| M8 | M, R | LC-MS/MS, NMR | Pre-MAC of UD | 417, 395 | 274, 298, 316, 359, 377 |
| M9 | M, R | LC-MS/MS, NMR | Pre-MAC of UD | 417, 395 | 274, 316, 359, 377 |
| M10 | D | LC-MS/MS | Sulfate conjugate of hydroxyl UD | 312, 329, 346 | 294 |
| M11 | M, R, D | LC-MS/MS, NMR | Sulfate conjugate of 3-hydroxy UD | 312, 329, 346 | 294 |
| M12a,b * | M, R, D | Hydrolysis | A mixture of glucuronides of CMA and 2-chlorophenylglycine | ||
| M13 | M, R, D | LC-MS/MS | Sulfate conjugate of hydroxy UD | 312, 329, 346; | 294 |
| M14 * | M, R, D | Cochromatography, LC-MS/MS | R338228, N-acetyl dervative of 2-chlorophenylglycine | 228 | 140, 169, 182, 186, 210 |
| M16 | D | Hydrolysis, LC-MS/MS of M11 | 3-hydroxy UD | ||
| M18 | R, D | Hydrolysis, LC-MS/MS | Glucuronide of M25 | 347 | 84, 85, 113, 157, 175, 210 |
| M19 | R | Hydrolysis, LC-MS/MS | Glucuronide of M25 | 347 | 84, 85, 113, 157, 175, 210 |
| M20 | M, D | LC-MS/MS | Sulfate conjugate of hydroxyl UD | 312, 329, 346 | 294 |
| M21 * | M, R, Rb, D | Cochromatography, Hydrolysis, LC-MS/MS | R289876, glucuronide of UD | 409 | 198, 216, 374, 392 |
| M22 * | M, R | Cochromatography, LC-MS/MS | R300592, 4-hydroxy UD | 230 | 211, 169, 230 |
| M23 * | M, Rb, D | LC-MS/MS, NMR, chiral analysis, cochromatography | O-Glucuronide of RWJ-452399 (the other enantiomer of UD) | 409, 392 | 198, 216, 374, 392 |
| M24 | M, R, Rb | LC-MS/MS, NMR | Sulfate conjugate at the alcohol function of UD and/or of its enantiomer | 330, 313, 295 | 119, 137, 155, 198, 238, 233, 216 |
|
M25
*
| R | Cochromatography | R288223, 1-chloro-2-(1,2-dihydroxyethyl)benzene |
|
|
MA, molecular adduct of NH3+ or Na+.
↵* Identified with synthetic reference standard.