Mass spectral data on imatinib and its metabolites in plasma, urine and feces Data are from LC-MS runs of isolated imatinib and metabolites. Components are listed in the order of elution. Proposed chemical structures are shown in Table 4: electrospray ionization, positive ion mode, upfront collision offset (cone voltage) of 30, 40, and 80 V (combined data), and single-stage mass separation. Some of the expected fragment ions may be missing because of low intensities and/or high background of coeluting endogenous components.
Component | Matrixa | Observed Ions | Shift of M + H+ Ion Upon H/D Exchangeb | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M+H+c | [M+2H]2+ | M+H+-H2O | Frag. Ad | Frag. Bd | Frag. Cd | Frag. Dd | Frag. Ed | Additional Ions | |||||||||||
| m/z | m/z | ||||||||||||||||||
| M20.0a | U(P) | 656 | 328.6 | 394 | 276 | 262 | 222 | 203 | 678e, 502e, 480f, 379 | +7 | |||||||||
| M21.0 | P(U) | 670 | 335.7 | 394 | 276 | 262 | 222 | 217 | 692e, 516e, 494f, 379 | +6 | |||||||||
| AFN911 | F(P, U) | 510 | 492 | 217 | 532e, 393, 392 (Frag. A-H2O), 364, 274 (Frag. B-H2O) | +4 | |||||||||||||
| CGP74588 | F(P, U) | 480 | 240.6 | 462 | 394 | 276 | 262 | 222 | 203 | 502e, 379, 351, 290, 247 | +4 | ||||||||
| M23.7 | U | 684 | 394 | 706e, 530e, 508f, 249 (Frag. E + H2O) | +6 | ||||||||||||||
| Imatinib | F(P, U) | 494 | 247.6 | 476 | 394 | 276 | 262 | 222 | 217 | 516e, 379, 351, 290, 247 | +3 | ||||||||
| M25.6 | U | 670 | 394 | 217 | 516e, 494f | +7 | |||||||||||||
| M27.6 | U | 684 | 394 | 231 | 706e, 530e, 508f | +6 | |||||||||||||
| CGP72383 | U(P) | 510 | 255.6 | 492 | 410 | 217 | 532e, 392, 276 (Frag. B-O), 262 (Frag. C-O), 189 | +3 | |||||||||||
| APG049 | F(P, U) | 494 | 476 | 394 | 222 | 217 | 516e, 379, 290, 264, 235 (Frag. E + H2O) | +4 | |||||||||||
| M28.8 | U | 494 | 476 | 394 | 217 | 516e, 379 | N.D. | ||||||||||||
| M29.6 | F(P, U) | 508 | 490 | 394 | 276 | 262 | 222 | 231 | 530e, 480, 437, 423, 379, 203 | +3 | |||||||||
| CGP71422 | U(P, F) | 510 | 255.6 | 394 | 276 | 262 | 532e, 450, 435, 423, 395, 393, 277 | +2/+3g | |||||||||||
| APG050 | F(P, U) | 508 | 490 | 394 | 222 | 231 | 530e, 480, 379, 249 (Frag. E + H2O), 203 | +3 | |||||||||||
| M42.2 | F(U) | 426 |
| 408 |
|
|
|
| 149 | 448e, 380, 261 | +4 | ||||||||
-
N.D., not determined. H/D exchange, hydrogen-deuterium exchange. Nomenclature of fragment ions of imatinib and its metabolites is illustrated as follows (imatinib as example):
-
↵ a P, plasma, U, urine, F, feces; spectrum in the table obtained after isolation from the matrix in boldface; essentially same spectrum obtained after isolation from matrix/matrices in parentheses
-
↵ b Equal to number of heteroatom-bound hydrogens in the neutral molecule plus one
-
↵ c Measured exact mass in agreement with proposed structure
-
↵ d In the case of glucuronides, Fragments A through E refer to the aglycone formed in the mass spectrometer by loss of anhydroglucuronic acid
-
↵ e Sodium adduct
-
↵ f Aglycone of M+H+
-
↵ g Incomplete H/D exchange, same observation for authentic reference compound
