Metabolites of VPA and α-fluoro VPA detected in the urine of micea,b
| Compound | Drug in Urine after Hydrolysis (μmol)2-c | Drug in Urine before Hydrolysis (μmol) | Estimated Glucuronide (μmol)2-d | Glutamine Conjugate (μmol) |
|---|---|---|---|---|
| VPA | 14.4 ± 0.1 | 7.3 ± 1.1 | 7.1 | N.D. |
| (E)-2-Ene VPA2-e | 0.09 ± 0.01 | 0.07 ± 0.01 | 0.03 | N.D. |
| α-Fluoro VPA | 12.8 ± 1.3 | 11.9 ± 1.4 | 0.8 | 8.3 ± 1.1 |
2-a The urine samples were collected during a 24-hr period after the administration of VPA or α-fluoro VPA at 0.83 mmol/kg.
2-b Drugs and their metabolites recovered in the urine were expressed as mean ± S.D. (n = 4). N.D., Not detected under the LC/MS/MS conditions used.
↵2-c The hydrolysis of urine samples was carried out at pH 12.5, 60°C for 1 hr.
↵2-d Urinary glucuronides were estimated from the differences in free drug concentrations between the hydrolyzed and unhydrolyzed samples.
↵2-e The phase I metabolite (E)-2-ene VPA was detected only in the urine of mice treated with VPA.