TABLE 1

LC-MS comparison of temsirolimus metabolic products from human liver microsomes and from recombinant CYP3A4


Products from HLM (Retention Time)a

[M-H]m/zb

Products from CYP3A4 (Retention Time)a

[M-H]m/zb
Peak 1-2 (29.8-31.2 min) 1060, 1058 Peak 1-2 (31.0-31.9 min) 1060, 1046
Peak 3-4 (35.7-36.2 min) 1060, 1046, 1014 Peak 3 (32.4 min) 1030
Peak 5 (3638.2 min) 1030 Peak 4 (35.7 min) 1014
Peak 6 (40.1 min) 1026 Peak 5-6 (38.3-39.8 min) 1026, 1028
Seco-temsirolimus (43.9 min) 1028 Seco-temsirolimus (44.1 min) 1028
Peak 7 (47.0 min) 1030 Peak 7 (47.6 min) 1030
M8 (54.5 min) 1044 M8 (54.6 min) 1044
M9 (58.0 min) 1044 M9 (58.3 min) 1044
M10 (61.2 min) 1044 M10 (61.8 min) 1044
M11 (64.4 min) 1044 M11 (64.9 min) 1044
Peak 11′ (66.2 min) 1030
M12 (69.8 min) 1044 M12 (69.8 min) 1044
M13 (83.3 min) 1014 M13 (83.1 min) 1014
M14 (87.4 min) 1028
Temsirolimusc (87.9-90 min)
1028
Temsirolimus (88.2-90 min)
1028
  • a Retention time in semipreparative HPLC.

  • b All in negative ESI MS.

  • c As for rapamycin, temsirolimus exists in two isomer forms in solution.