Table 3.

Fragment ions and relative amounts for apremilast metabolites characterized in plasma, urine and faeces.

Metabolite Characterization				Plasma (% AUC relative to TRA)d	% of dose excreted
Number	Pathway	[M + H]+a	Fragment Ions		Urine	Faeces
Apremilast	Unchanged	461	257,205, 178, 163, 150	44.8	2.8	4.1
M1/M2	Hydrolysis products of apremilast	479	274, 257, 223, 206, 178	D	0.9	0.5
M3	O-Demethylation	447	243, 164, 136	D	D	4.6
M4	O-Demethylation, N-deacetylation	405	243,164	ND	ND	2.4
M7	N-Deacetylation	419	257, 178, 163	D	D	0.1
M8	Hydroxylation, O-demethylation, N-deacetylation	421	243, 179, 164	ND	ND	1.0
M9	Hydrolysis product of M3	465	260, 243, 223, 206, 164	ND	ND	7.7
M10	Hydroxylation, O-demethylation	463	243,221, 164, 163, 136	ND	ND	1.3
M11	Hydroxylation, N-deacetylation	435	257, 179, 178	2.5	ND	1.4
M12	O-Demethylation, glucuronidation	623	447, 243	38.7	33.7	ND
M13	O-Deethylation, glucuronidation	609	488, 433, 229, 205, 150	2.4	2.0	ND
M14	O-Demethylation, N-deacetylation, glucuronidation	581	405, 243	4.9	4.0	ND
M15	Hydrolysis product of M12	641	465, 436, 260, 243, 164	ND	3.3	ND
M16	Hydroxylation, glucuronidation	653	477,397,257	6.6	0.6	ND
M17	Hydroxylation	477	257,221, 178, 163	D	1.2	0.9
M18	Hydrolysis	222°	178, 136, 134, 92	ND	ND	1.4
M19	O-Demethylation, O-deethylation	419	215,205, 163, 136	ND	ND	0.8
M20b	O-Demethylation, O-deethylation, N-deacetylation	377	215, 163, 136	ND	ND	0.5
M21b	Hydroxylation, O-demethylation, O-deethylation	435	221,215, 163, 136	ND	ND
M22	Hydrolysis, O-deethylation	451	246, 229, 223, 206, 150, 135	ND	ND	0.6
M23	Hydrolysis, hydroxylation	238c	194, 150, 136, 92, 74	ND	ND	3.0

ND, not detected; D, detected by MS, but at concentrations too low to accurately quantify by radiochromatography.

^aMany compounds were observed as [M + H]⁺ and [M + NHJ⁺.

^bM20 and M21 coeluted under the HPLC conditions used.

^cCharacterized in negative mode, so values are [M - H]∼

^dAUC_0-t) (unchanged drug or metabolite)/AUC₀_₄₈ (TRA) * 100%.