Monitoring 2-ethyl-2-phenylmalonamide in serum by gas-liquid chromatography: application to retrospective study in epilepsy patients dosed with primidone.

We describe a procedure for determining 2-ethyl-2-phenylmalonamide (I) in serum of epilepsy patients dosed with primidone (II) for seizure control, by extracting the sample with chloroform under basic conditions, with use of an internal standard, 2-ethyl-2-(p-tolyl)malonamide, and without derivative formation. The sensitivity limit is 1.0 mg/L. Within-run CVs for 5, 10, and 30 mg/L concentrations were 3.5, 2.5, and 0.7%, respectively. For a 1.0 mg/kg body wt per day dose of II in patients co-medicated with phenytoin (Group A), the mean steady-state concentrations of I, II, and phenobarbital (III) were 0.72, 0.62, and 2.24 mg/L, respectively. For patients co-medicated with carbamazepine and phenytoin (Group B), I, II, and III concentrations were 0.68, 0.44, and 2.12 mg/L, respectively. Between these groups, only for II were the concentrations statistically different (t = 2.762; p < 0.01). For Group A no correlation was found between II and III. For Groups A and B, the coefficients of correlation between I and III were 0.626 and 0.826, respectively.