TABLE 4

Metabolites of S-1 identified in rat feces of 0 to 24 h (using mobile phase system 2)

Numbers in bold are values of m/z for basic mass peaks in the corresponding MS spectrum.

Metabolite Identification
Retention Time
[M — H]—
MS/MS
Sites of Biotransformation or Confirmed Structure
min m/z m/z
1* 26.62 213 111 3-(4-Fluorophenoxy)-2-hydroxy-2-methyl-propanoic acid
9 29.40 467 387, 127; MS3 of 387→259, 201, 175 127; MS4 of 259→229, 209, 201, 175 Nitro reduction, mono-hydroxylation on the B-ring and sulfation
17 32.34 387 259, 127; MS3 of 259→201, 175 Nitro reduction and mono-hydroxylation on the B-ring
12 32.55 467 387, 127; MS3 of 387→259, 201, 175 127; MS4 of 259→230, 201, 175 Nitro reduction, mono-hydroxylation on the B-ring and sulfation
6 38 301 221; MS3 of 221→191, 171 Mono-hydroxylation on 4-nitro-3-trifluoromethyl-phenylamine and sulfation
38 38.14 467 387, 127; MS3 of 387→259, 201, 175 127; MS4 of 259→229, 209, 201, 175 Nitro reduction, mono-hydroxylation on the B-ring and sulfation
21 39.01 387 259, 201,127; MS3 of 259→229, 201, 175 Nitro reduction and mono-hydroxylation on the B-ring
39 40.18 451 371; MS3 of 371→259, 231, 201, 175, 111; MS4 of 259→201, 175 Nitro reduction and sulfation
29 44.84 387 259, 127 Nitro reduction and mono-hydroxylation on the B-ring
31 45.52 387 275, 255, 111; MS3 of 275→255 Nitro reduction and mono-hydroxylation on the A-ring or phenylamine on the A-ring
32 47.19 371 259, 231, 201, 175, 111; MS3 of 259→229, 201, 175 Nitro reduction
24 50.01 577 401, 307, 261, 205, 175 Glucuronidation of S-1
40
52.56
307
289, 245, 205; MS3 of 289→245, 204
O-Dephenylation (the B-ring) {2,3-dihydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)-phenyl]-propanamide}

  • ↵* indicates that the structure of the metabolite has been confirmed using a synthetic standard in LC-MSn.