(S)-Warfarin → 40281-89-8
Reaction equation
[CH3:1][C:2]([CH2:4][C@H:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]=1[OH:23])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:3].[CH3:24][C:25]([CH:27]([OH:47])[CH:28]([C:35]1[C:44](=[O:45])[O:43][C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]=1[OH:46])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>>[CH3:1][C:2]([CH2:4][C@@H:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[OH:23])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:3].[CH3:24][C:25]([CH:27]([OH:47])[CH:28]([C:35]1[C:44](=[O:45])[O:43][C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]=1[OH:46])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26]Participants
Procedure
The microsomal incubations with R and S-warfarin clearly demonstrate the formation of all four 10-hydroxywarfarin isomers by human liver microsomes (FIG. 4). Incubations with R-warfarin (FIG. 7) produced two product peaks with the 10-hydroxywarfarin specific SRM as observed at 7.06 and 7.74 min at a ratio of 1:10 (25 μM reaction) or 1:18 (500 μM reaction). The presence of two peaks confirms the addition of a second chiral center of 10-hydroxywarfarin (FIG. 4). Similarly, two 10-hydroxywarfarin product peaks were observed for incubations with S-warfarin, eluting at 7.37 and 8.03 min at a 1.7:1 (25 μM reaction) or 1.6:1 (500 μM reaction) ratio. These two peaks further confirm the presence of a second chiral center on 10-hydroxywarfarin. For biomonitoring purposes we therefore assigned the 1st and 3rd peaks as 10-hydroxywarfarin metabolites derived from R-warfarin and the 2nd and 4th peaks as 10-hydroxywarfarin derived from S-warfarin. This appears to be the first report of separation and quantitation of all four 10-hydroxywarfarin isomers.
Sources & evidence
- ORD record
- ord-c0db5d06050344fca752610941725c0f
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08608967B2
Reaction notes
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