M12 | M15 | M16 | M17 | M18 | M19 | M20 | Fingolimod | |
---|---|---|---|---|---|---|---|---|
Retention time (min) | ||||||||
HPLC conditions 1a | 34.7 | 34.3 | 34.3 | 34.3 | 34.6 | 35.8 | 36.2 | 41.9 |
HPLC conditions 3b | 35.7 | 35.4 | 35.4 | 35.4 | 35.7 | 36.8 | 37.2 | 42.7 |
HPLC conditions 4b | 32.1 | 31.8 | 32.3 | 32.1 | 32.9 | 34.3 | 34.8 | 42.4 |
Relative abundance of metabolites (%)c | ||||||||
HLM | 1.40 | 0.43 | ||||||
CYP2D6 | 1.02 | 1.88 | 1.17 | 1.02 | ||||
CYP2E1 | 2.11 | |||||||
CYP3A4 | 0.11 | 0.19 | 0.19 | 0.38 | 0.22 | 1.09 | ||
CYP4F2 | 2.99 | 0.31 | ||||||
CYP4F3B | 0.84 | |||||||
CYP4F12 | 1.19 | 1.79 | ||||||
Control (insect cell)d |
↵a Conditions of HPLC runs with radioactivity detection (see experimental part).
↵b Conditions of LC-MS runs (see experimental part).
↵c Relative abundance: percentage of total radioactivity in incubate. Incubates of [14C]fingolimod (20 μM for CYP2D6, CYP2E1, CYP3A4, and HLM or 100 μM for CYP4F2, CYP4F3B, CYP4F12, and insect cell control) for 30 min with 0.56 mg protein/ml (HLM), 150 pmol P450/ml (recombinant enzymes), or 0.75 mg protein/ml (insect cell control).
↵d None of the metabolites M12 or M15 to M20 detected.