TABLE 3.
Summary of the metabolites of (+)-9-trifluoroethoxy-α-dihydrotetrabenazine [(+)-13e] detected in human, dog and rat liver microsomes and in dog plasma using the UPLC-Q Exactive™ Orbitrap HRMS.
| No | TR min | Theonetical Mass m/z | Experimental Mass m/z | Error ppm | Fomula [M + H]+ | Fragment ions m/z | Identification/Reaction | Relative abundance, UV area % | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Human | Dog | Rat | ||||||||
| Liver microsomes | ||||||||||
| M403-1 | 5.36 | 404.2043 | 404.2036 | -1.7 | C20H29F3NO4 | 386, 358, 286, 260, 233 | Mono-oxidation | 0.72* | 1.27 | 0.48* |
| M403-2 | 5.59 | 404.2043 | 404.2037 | -1.5 | C20H28F3NO4 | 386, 368, 312, 260, 233 | Mono-oxidation | 12.11 | 10.01 | 8.78 |
| M373 | 6.34 | 374.1938 | 374.1931 | -1.9 | C19H26F3NO3 | 356, 328, 273, 246 | Demethylation | 0.69* | 0.46* | 2.6 |
| M385 | 7.98 | 386.1938 | 386.1929 | -2.3 | C20H26F3NO3 | 368, 342, 312, 260 | Dehydrogenation | 1.02 | 1.15* | 3.18 |
| P | 8.48 | 388.2094 | 388.2087 | -1.8 | C20H29F3NO3 | 370, 342, 286, 233 | NA | 85.31 | 87.01 | 84.91 |
| Dog plasma | Identification/Reaction | UV area % | ||||||||
| M565 | 7.17 | 566.2208 | 566.2203 | -0.9 | C25H34O10NF3 | 548, 390, 372, 354, 298, 246 | Mono-oxidation,demethylation andglucuronidation | 10.2 | ||
| M579-1 | 12.04 | 580.2364 | 580.2355 | -1.6 | C26H36O10NF3 | 562, 404, 386, 368, 312, 260 | Mono-oxidation andglucuronidation | 3.43 | ||
| M579-2 | 12.88 | 580.2364 | 580.2357 | -1.2 | C26H36O10NF3 | 404, 386, 358, 260 | Mono-oxidation andglucuronidation | + | ||
| M549 | 13.01 | 550.2258 | 550.2251 | -1.3 | C25H34O9NF3 | 532, 374, 356, 328, 273, 219 | Demethylation andglucuronidation | 7.47 | ||
| M403-1 | 14.46 | 404.2043 | 404.2038 | -1.2 | C20H28O4NF3 | 386, 358, 286, 260, 233 | Mono-oxidation | 1.47 | ||
| M403-2 | 15.06 | 404.2043 | 404.2039 | -1.0 | C20H28O4NF3 | 386, 368, 312, 260, 233 | Mono-oxidation | 9.69 | ||
| M563 | 16.92 | 564.2415 | 564.2409 | -1.1 | C26H36O9NF3 | 388, 370, 342, 286, 233 | Glucuronidation | 9.92 | ||
| P | 20.86 | 388.2094 | 388.2089 | -1.3 | C20H28O3NF3 | 370, 342, 286, 260, 233 | NA | 57.3 | ||
*, It is the relative abundance detected by mass spectrometry, and there is no the peak in UV, detection, and the relative abundances of other peaks detected by the two detectors are similar.
Theoretical Mass (m/z) = Exact Mass +1.0073 (H+); Exact Mass: Monoisotopic Mass; Error (ppm) = [(Measured Mass - Theoretical Mass) ÷Theoretical Mass]×106; NA: not applicable.