TABLE 4

List of metabolites and their proposed chemical structures Structures of imatinib metabolites partially or completely characterized by LC-MS (labeled as Mxx.x) and/or by comparison with authentic reference compounds (labeled with corresponding compound codes) are given below. The components are listed according to the site and type of metabolic reaction (from changes in the non-piperazine moiety to changes in the piperazine substructure). Systemic exposure to imatinib and its metabolites in plasma (P) is expressed as AUC0-24 h in μmol·h/l, and percentage of total [14C]AUC0-24 h is given within parentheses. Radiolabeled components detected in urine and feces are indicated as U and F. Amounts of imatinib and its metabolites in urine (0-72 h) and feces (0-168 h) are given in percentage of administered dose. Proportions of coeluting components could only be roughly estimated. For metabolites M19.8, M20.0b, M21.4, M21.6, M22.8, M23.6, M24.0, M25.2, M26.4, M26.8, M27.8a, M27.8b, M29.2, M31.0, M39.4, and M39.8 in plasma, urine, and/or feces (Figs. 3, 4, 5), only partial structures could be determined (U. Pfaar, M. Zollinger and H.-P. Gschwind, unpublished data).


Site and Type of Metabolic Reaction

Compound Name and Presence in Matrix
Chemical Structure
R=CH3
R=H
Embedded Image Imatinib (parent drug) CGP74588 (main metabolite)
P, 17.7 (70) P, 2.4 (9.5)
U, 5.0; F, 23 U, <1.8; F, <11
M21.0 (glucuronide) M20.0a (glucuronide)
P, 1.0 (4.0) P, <0.4 (<1.6)
U, ≤0.4 U, ≤0.2
Embedded Image CGP72383
P, 0.29 (1.1)
U, ≤0.3
Embedded Image AFN911
P, <0.22 (<0.9)
U, ≤0.4; F, ≤2
Embedded Image CGP71422
P, <0.21 (<0.8)
U, <0.3; F, ≤0.3
Embedded Image APG050 APG049
P, 0.32 (1.2) P, 0.11 (0.4)
U, ≤1.5; F, <0.3 U, 0.1; F, 1.6
M23.7 (glucuronide)
U, ≤0.3
Embedded Image M29.6 M28.8
P, <0.21 (<0.8) U, <0.1
U, <0.3; F, ≤1
M27.6 (glucuronide) M25.6 (glucuronide)
U, ≤0.3 U, ≤0.5
Embedded Image M42.2

U, 0.1; F, 1.3