In vitro phase-I and reactive metabolites of X-376.

	MS scan	Most abundant fragment ions	Rt.a (min)	Metabolic reaction
X-376	547	447, 357, 257, 138	38.9	Main drug
Phase-I metabolites
M1	533	447, 343, 257, 138	38.0	N-Demethylation at the piperazine ring
M2	549	449, 359, 259, 139	35.6	Reduction metabolic reaction in the amide group attached to the pyridazine ring
M3	561	447, 371, 257, 138	44.1	Oxidation at the piperazine ring
M4	563	447, 373, 257, 138	42.0	Hydroxylation at the piperazine ring
Reactive metabolites
M5	572	472, 282, 120, 104	39.2	Cyano addition at the pyridazine ring
M6	588	472, 282, 104	42.9	Hydroxylation at the piperazine ring and cyano addition at the pyridazine ring
M7	852	496, 357, 257, 176	28.9	Defluorination, hydroxylation, oxidation, and GSH conjugation

^aRt., retention time.