TABLE 5

Concentration and AUC data of catabolites in serum

Concentrations (nanomolar) and pharmacokinetic parameters of metabolites in serum of tumor-bearing nude rats following a single intravenous administration of nominal 10 mg/kg [³H]DM1-LNL897. Data were derived from SEC-LC with off-line radiodetection obtained after injection of extracted serum.

Metabolite/Component	Sample Collection Time				Exposure
Metabolite/Component	1 Hour	24 Hours	96 Hours	168 Hours	AUC_0–168h	Percentage of AUC_0–168h	AUC_inf
	nM	nM	nM	nM	nM·h	%	nM·h
P1 (front peak)	5.81	2.47	0.754	0.215	249	0.395	262
P1.8 (front peak)	0.700	0.408	0.158	0.0321	40.3	0.0640	42.1
M7 (cysteine conjugate)	1.58	0.515	0.166	0.0463	57.1	0.0907	59.9
M2^a (LYS-MCC-DM1)	ND	0.408	0.232	0.0676	38.5	0.0611	42.5
M6 (Maysine)	1.06	0.419	0.116	0.0248	41.9	0.0664	43.1
M1^a (MCC-DM1)	1.72	0.327	ND	ND	36.2	0.0575
M5 (derivatized DM1)^b	16.3	2.93	0.821	0.189	400	0.635	410
Sum of additional metabolites^c	2.23	0.199	0.230	0.0895	56.0	0.0888	60.6
Total components detected	13.1	4.74	1.66	0.475	519	0.824	549
Lost during sample processing^d	1443	588	205	67.4	62,469	99.2	NC
Total components in original sample	1456	593	207	67.9	62,988	100	67,500

NC, not calculated; ND, not detected.
↵^a Peaks were identified by retention time only.
↵^b DM1-NEM measured after TCEP treatment is shown in italic (corresponds to possible disulfide-bonded DM1 with endogenous components in serum).
↵^c Corresponds to the sum of the residual RA measured in each radiochromatogram.
↵^d Including ADCs and/or aggregates/complexes.