Table 3.
Assignment, proposed structures, and MS/MS characteristics of major metabolites identified following incubation of either human liver microsomal fractions (1 mg/mL final concentration; in the absence or presence of either 1 mmol/L NADPH or 3 mmol/L UDPGA), recombinant human isoforms (CYPs, FMOs, MAO, and UGTs) or human hepatocytes (pool of four preparations in the absence or presence of CYP and MAO inhibitors) with dronedarone and its metabolites (5 μmol/L final concentration)
Assignment | Rt (min) | Metabolite description | Theoretical MH+ (m/z) | Measured MH+ (m/z) | ΔM ppm | Elemental composition MH+ (m/z) | Product ions (m/z) |
---|---|---|---|---|---|---|---|
M1 | 19.5 | Hydroxy phenol-dronedarone glucuronide | 580.14832 | 580.14879 | 0.806 | C26H30NO12S+ | 121, 386, 404 |
M2 | 20.0 | C-dealkyl-dronedarone | 308.22202 | 308.22217 | 0.486 | C18H30NO3+ | 114, 170, 252 |
M3 | 20.7 | Hydroxy phenol-dronedarone glucuronide | 580.14832 | 580.14836 | 0.065 | C26H30NO12S+ | 121, 386, 404 |
M4 | 22.6 | Hydroxy N-debutyl-dronedarone | 517.23668 | 517.23650 | −0.356 | C27H37NO6S+ | 86, 114, 386 |
M5 | 23.3 | Oxidized N-debutyl-dronedarone | 515.22103 | 515.22180 | 1.487 | C27H35N2O6S+ | 86, 114, 308 |
M6 | 23.4 | Dihydroxy-dronedarone | 589.29420 | 589.29528 | 1.835 | C31H45N2O7S+ | 158, 186, 467 |
M7 | 23.8 | Hydroxy N-debutyl-dronedarone | 517.23668 | 517.23638 | −0.588 | C27H37N2O6S+ | 86, 114, 294, 386 |
M8 | 25.2 | Hydroxy phenol-dronedarone | 404.11623 | 404.11663 | 0.979 | C20H22NO6S+ | 121 |
M9 | 25.7 | Hydroxy, oxidized propanoic acid-dronedarone | 490.11663 | 490.11684 | 0.432 | C23H24NO9S+ | 193 |
M10 | 25.8 | Hydroxy propanoic acid-dronedarone | 476.13736 | 476.13742 | 0.118 | C23H26NO8S+ | 193 |
M11 | 26.7 | Hydroxy propanoic acid-dronedarone | 476.13736 | 476.13727 | −0.197 | C23H26NO8S+ | 193 |
M12 | 26.9 | Hydroxy dronedarone | 573.29928 | 573.29883 | −0.792 | C31H45N2O6S+ | 114, 142, 170, 451, 517 |
M13 | 27.1 | N,N′-Didebutyl dronedarone | 445.17917 | 445.17947 | 0.676 | C23H29N2O5S+ | 58, 294, 388 |
M14 | 27.4 | Hydroxy dronedarone | 573.29928 | 573.29895 | −0.583 | C31H45N2O6S+ | 114, 142, 170, 386, 451, 517 |
M15 | 27.6 | O-dealkylation hydroxyl dronedarone | 404.11623 | 404.11586 | −0.927 | C20H22NO6S+ | 121, 292 |
M16 | 28.3 | Hydroxy N-debutyl-dronedarone | 517.23668 | 517.23676 | 0.108 | C27H37N2O6S+ | 102, 130, 294, 388 |
M17 | 29.1 | Dihydroxy-dronedarone | 589.29420 | 589.29326 | 1.593 | C31H45N2O7S+ | 174, 202, 294, 451 |
M18 | 29.2 | Hydroxy phenol-dronedarone | 404.11623 | 404.11639 | 0.385 | C20H22NO6S+ | 121, 292 |
M19 | 29.9 | Phenol-dronedarone glucuronide | 564.15341 | 564.15289 | −0.918 | C26H30NO11S+ | 121, 294, 388 |
M20 | 30.2 | Hydroxy propanoic acid-dronedarone | 476.13736 | 476.13782 | 0.958 | C23H26NO8S+ | 193, 292, 458 |
M21 | 31.4 | N-debutyl-dronedarone | 501.24177 | 501.24172 | −0.099 | C27H37N2O5S+ | 86, 114, 294, 388 |
M22 | 32.4 | Hydroxy dronedarone | 573.29928 | 573.29924 | −0.077 | C31H45N2O6S+ | 158, 186, 294, 451 |
M23 | 32.8 | Deaminated N,N′-didebutyl dronedarone glucuronide | 622.19527 | 622.19434 | −1.499 | C29H36NO12S+ | 294, 446 |
PD | 36.3 | Dronedarone | 557.30437 | 557.30437 | 0.001 | C31H45N2O5S+ | 114, 142, 170, 294, 435, 501 |
M24 | 38.5 | Phenol-dronedarone | 388.12132 | 388.12152 | 0.515 | C20H22NO5S+ | 121, 294 |
M25 | 39.1 | Propanoic acid-dronedarone | 460.14245 | 460.14296 | 1.110 | C23H26NO7S+ | 193, 294 |
M26 | 39.5 | Deaminated N,N′-didebutyl dronedarone | 446.16318 | 446.16387 | 1.536 | C23H28NO6S+ | 121, 179, 294 |
HRMS, high-resolution mass spectrometry; Assignment, assignment; Rt, retention time; PD, parent drug.