Analytical Specificity of Commercially Available Methods for Serum Phenytoin Determination

Phenytoin concentrations in serum obtained from uremic patients and patients with normal renal function were measured by fluorescence polarization immunoassay (FPI), rate nephelometric inhibition immunoassay (RNII), and homogeneous enzyme immunoassay (EIA) and compared to corresponding values determined by high performance liquid chromatography (HPLC). In serum specimens from patients with normal renal function, phenytoin concentrations measured by FPI, RNII, and EIA averaged within 12% of the corresponding concentrations determined by HPLC. Phenytoin concentrations in uremic serum were 20% (FPI), 60% (EIA), and 83% (RNII) higher than corresponding values determined by HPLC. Accumulation of phenytoin metabolites in patients with end-stage renal disease was associated with artifactually elevated measured serum concentrations of phenytoin. FPI was the most specific of the three commercial methods evaluated.