TABLE 2

Tienilic acid and its analogs plus the metabolites formed when incubated with cytochrome P450 2C9, reduced nicotine adenine dinucleotide triphosphate, and glutathione

The molecular ion ([M+H]+), fragment ions, and metabolic reactions of each analyte are shown.

ParentMetabolite NameAssignment[M+H]+Fragment Ions Metabolic Reaction
m/z
Tienilic acid Parent331285, 247, 201, 189, 111
TA-M1TA + GSH636561, 507, 490, 361, 247, 189GSH conjugation pathway A
TA-M2TA + O347301, 273, 247, 201, 189, 127Hydroxylation
TA ethyl ester TA-EE359330, 285, 247, 201, 111
TA-EE M1TA330285, 247, 201, 189, 111 N-dealkylation
TA-EE M2TA-EE + GSH + 2H666648, 537, 519, 247, 189GSH conjugation pathway B
Methoxyl analog of TA Parent287203, 111
TA-OMe M1TA-OMe + GSH592517, 463, 446, 360, 317, 203GSH conjugation pathway A
TA-OMe M2TA-OMe + GSH + 2H594501, 447, 429, 401, 308, 203, 189GSH conjugation pathway B
TA-OMe M3TA-OMe + O303203, 127Hydroxylation
TA n-propyl alcohol Parent331313, 285, 273, 247, 229, 189, 111
TA-OnPA M1TA-OnPA + GSH + 2H638620, 545, 491, 473, 416, 388, 247, 189GSH conjugation pathway B
TA-OnPA M2TA-OnPA − (C3H7)289189, 161, 127Dealkylation and thiophene oxidation
TA-OnPA M3TA-OnPA − (C2H7O)273189, 127Dealkylation
TA ethyl amide Parent358331, 313, 285, 273, 189, 111
TA-EA M1(TA-EA) + GSH663588, 534, 517, 431, 388GSH conjugation pathway A
TA-EA M2(TA-EA) − C2H5 330313, 285, 273, 189, 111 N-dealkylation
TA diethylamide Parent386350, 313, 285, 229, 201, 111
TA-DiEA M1(TA-EA) + GSH691673, 616, 562, 545, 459, 416, 381, 302GSH conjugation pathway A
TA-DiEA M2(TA-EA) − C2H3 358313, 285, 273, 229, 189, 111 N-dealkylation
3-Thenoyl regioisomer of TA Parent331287, 247, 189, 111
TAI M1TAI + GSH + H638563, 509, 308,179GSH conjugation + addition of 2H
TAI M2TAI + O + GSH652523, 505, 469, 377, 247GSH conjugation + oxygen addition
TAI M3TAI + GSH636561, 507, 490, 404, 361, 247GSH conjugation
TAI M4TAI+O347301, 273, 247, 201, 189, 127hydroxylation
5-Methyl TA Parent345299, 247, 201, 189, 125
5-MeTA M15-MeTA + O361343, 315, 247, 189Hydroxylation
Phenyl isomer of TA Parent325279, 247, 189, 105
PA M1PA + GSH + H2O648630, 555, 501, 483, 355, 306, 177GSH conjugation via epoxidation
PA M2PA + GSH + H2O648630, 555, 501, 483, 355, 306, 177GSH conjugation via epoxidation
PA M3PA+O341295, 247, 201, 189, 121Hydroxylation
PA M4PA+O341295, 247, 201,189, 121Hydroxylation
5-Chloro TA Parent365319, 245, 201, 189, 145
5-ClTA M15-ClTA–Cl + GSH636561, 507, 490, 404, 361, 315, 247GSH conjugation via S-oxide