Contribution of 5-(4-Hydroxyphenyl)-5-phenylhydantoin to the Discrepancy Between Phenytoin Analyses by EMIT and High-Pressure Liquid Chromatography

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Abstract
Recently, phenytoin concentrations determined by enzyme multi-plied immunoassay technique (EMIT™) have been reported to be significantly elevated when compared to other assay methods in patients with end-stage renal disease (ESRD). We compared the plasma and plasma ultrafiltrate concentrations of phenytoin determined by EMIT and high-pressure liquid chromatography (HPLC) in a group of patients with normal renal function (NRF) and ESRD. The relationship between the degree of discrepancy in phenytoin concentrations in plasma and plasma ultrafiltrate and the concentration of combined (unconjugated plus conjugated) 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPHCom) was also assessed. The concentration of phenytoin in plasma and plasma ultrafiltrate measured by EMIT in the ESRD patients and the plasma ultrafiltrate concentrations of phenytoin in the NRF patients was significantly higher than the HPLC values. The mean concentrations of unconjugated HPPH (HPPHunconj) in plasma and plasma ultrafiltrate were not significantly different between the two patient groups. However, the concentration of HPPHCom in plasma and plasma ultrafiltrate specimens were significantly elevated in the ESRD patients. Orthogonal regression analysis of the relative error between the EMIT and HPLC phenytoin determinations and HPPHcom concentrations suggest that HPPHCom significantly correlates with the false elevation of phenytoin measurements in plasma and plasma ultrafiltrate. In patients with ESRD, phenytoin concentrations should be determined by either gas chromatography, HPLC, or fluorescence polarization.