Table 1. Summary of the Adducts Associated with PEX in Liver Microsomes and Human Primary Hepatocytes^a.

RT (min)	observed m/z [M + H]+	calculated m/z [M + H]+	mass error (ppm)	predicted molecular formula	identification	metabolite ID	source
10.96	418.1036	418.1036	0.00	C20H15ClF3N5	pexidartinib	PEX	HLM, MLM, PHH
8.86	723.1731	723.1722	1.24	C30H30ClF3N8O6S	PEX + GSH	M1	HLM, MLM, PHH
8.98	723.1731	723.1722	1.24	C30H30ClF3N8O6S	PEX + GSH	M2	HLM, MLM, PHH
8.48	739.1682	739.1672	1.35	C30H30ClF3N8O7S	PEX + O + GSH	M3	HLM, MLM
9.02	739.1677	739.1672	0.68	C30H30ClF3N8O7S	PEX + O + GSH	M4	HLM, MLM
9.58	739.1678	739.1672	0.81	C30H30ClF3N8O7S	PEX + O + GSH	M5	HLM, MLM
8.11	741.1839	741.1828	1.48	C30H32ClF3N8O7S	PEX + O + 2H + GSH	M6	HLM, MLM,
8.64	757.1783	757.1777	0.79	C30H32ClF3N8O8S	PEX + 2O + 2H + GSH	M7	HLM, MLM
6.27	559.1588	559.1581	1.25	C22H25ClF3N6O6S	cleaved right + GSH	M8	HLM, MLM
7.51	472.1055	472.1052	0.64	C18H22ClN5O6S	cleaved left + GSH	M9	HLM, MLM, PHH
3.88	582.1536	582.1532	0.69	C23H28ClN7O7S	amine + O + 2H + GSH	M10	HLM, MLM
8.53	594.1301	594.1296	0.84	C25H24ClF3N7O3S	PEX + Cys + Gly	M11	HLM, MLM, PHH
9.50	481.1363	481.1361	0.42	C21H20ClF3N6O2	PEX + O + 2H + NH2OMe	M12	HLM, MLM
10.82	463.1265	463.1261	0.86	C21H18ClF3N6O	PEX + NH2OMe-2H	M13	HLM, MLM
4.74	322.1065	322.1065	0.00	C14H16ClN5O2	amine + O + 2H + NH2OMe	M14	HLM, MLM
7.09	304.0959	304.0965	–1.97	C14H14ClN5O	amine + NH2OMe-2H	M15	HLM, MLM
10.87	311.1113	311.1114	–0.32	C14H13F3N4O	cleaved right + NH2OMeb	M16	HLM, MLM
12.41	205.0586	205.0583	1.46	C8H7F3N2O	nicotinaldehyde + NH2OMe	M17	HLM, MLM
12.24	210.0430	210.0429	0.48	C9H8ClN3O	cleaved left + NH2OMeb	M18	HLM, MLM

^aPEX, pexidartinib; GSH, glutathione; NH₂OMe, methoxyamine; O+, monohydroxylation; 2O+, dihydroxylation; O+2H+, monohydroxylation & hydrogenation; Cys, cysteine; Gly, glycine; HLM/MLM, human/mouse liver microsomes; PHH, primary human hepatocytes; Amine, N-dealkylated PEX.

^bSee Figure S1 for cleaved moieties.