TABLE 1

Results of LC-MS/MS analysis of in vitro incubations of [¹⁴C]MK-0767

Metabolite	m/z ^a	Fragment Ions, m/z	Retention Time	Occurrence^b
Metabolite	m/z ^a	Fragment Ions, m/z	Retention Time					RLM	DLM	MLM	HLM	3A4	RH	DH	MH	HH
			min
MK-0767	439	322, 264 (B),^c 193, 159, 148, 120	28.2	+	+	+	+	+	+	+	+	+
M3	631	455 (B), 437, 395, 280, 220	7.2						+		+
M5 ^d	444	336, 207, 205 (B), 192, 187, 166, 161, 159, 134	8.7						+	+	+
M7	443^e	379	8.7	+	+	+	+	+
M8	461	381, 364, 322, 310, 206, 189 (B), 135, 72	9.5	+	+	+	+	+		+
M9 ^d	444	336, 207, 205 (B), 192, 187, 166, 161, 159	9.8						+	+	+
M10 ^f	398	223 (B), 177	10.9	+				+	+		+
M11 ^f	354	179 (B), 159, 121	9.4	+	+	+	+	+	+	+	+	+
M12 ^d ^f	460	322, 285, 241 (B), 161, 159	11.7						+			+
M13 ^f	368	322, 193 (B), 159, 135	12.9	+	+	+	+	+	+		+	+
M15 ^d ^f	428	322, 253, 207 (B), 159, 14	17.1								+
M16 ^d	443	379, 362, 336, 268, 204 (B), 188, 161, 159	18.5	+	+	+	+		+	+	+	+
M18	397	352, 222, 177 (B), 159, 149	19.5	+	+	+	+	+	+		+	+
M19 ^f	340	165 (B), 159, 107	21.9	+	+	+	+	+	+			+
M20 ^d	459	442, 336, 322, 284 (B), 267, 204, 188, 161, 159, 149	22.9	+	+	+	+		+	+	+	+
M21 ^f	395	322, 220, 175 (B), 159, 149	23.8	+	+	+	+	+			+
M22 ^f	413	238, 193 (B), 161	24.6	+	+	+	+	+
M23 ^f	421	350, 246, 175 (B), 159	25.1	+	+	+	+	+	+		+	+
M24	455	395, 322, 280, 220, 175 (B), 159	25.3	+	+	+	+	+	+	+	+	+
M25 ^d	427	252, 235, 207 (B)	25.4		+	+	+		+		+	+
M26 ^f	338	163 (B), 159, 105	27.3	+	+	+	+	+	+	+	+	+
M27 ^f	437	262, 191 (B)	27.8	+	+	+	+	+	+	+	+	+
M28	425	308, 250 (B), 190, 179, 159, 134, 106	30.6	+	+	+	+		+

↵ a All [M + H]⁺, except as noted.
↵ b RLM, DLM, MLM, and HLM denote rat, dog, monkey, and human liver microsomes, respectively; 3A4, recombinant human CYP3A4; and RH, DH, MH, and HH represent rat, dog, monkey, and human hepatocyte suspensions, respectively.
↵ c B, base peak; +, detected by mass spectral analysis.
↵ d Metabolites formed in the presence of SAM and NADPH; all other metabolites were formed in the presence of NADPH.
↵ e [M - H]⁻.
↵ f Minor metabolites.