Oxaprozin and 5-(p-Hydroxyphenyl)- 5-phenylhydantoin Interference in Phenytoin Immunoassays

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Abstract
Rainey et al. (1) recently published their studies on metabolite and matrix interference in Abbott TDx® Phenytoin (TDx) and Phenytoin-II (TDxII) assays (Abbott Labs., Abbott Park, IL). They report that TDx Phenytoin, which uses a polyclonal antibody, demonstrates a substantial positive bias in patients with renal insufficiency because of the assay’s high (15.9%) cross-reactivity to the major metabolites of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) and its glucuronide ester (HPPG) (2). They also report that the TDxII assay, which uses a monoclonal antibody, has high (∼50%) cross-reactivity to a nonsteroidal anti-inflammatory drug, oxaprozin (Daypro®) (1). During a recent study, a patient taking oxaprozin demonstrated discrepancy between phenytoin values by the TDxII, which gave the result in the toxic range, and that by Chiron Diagnostics’ (Walpole, MA) new monoclonal assay, ACS:180® Phenytoin, for which the result was in the therapeutic range (GM Lawson, Mayo Clinic, personal communication).