Falsely elevated salicylate levels due to diflunisal overdose

A 33-year-old man ingested 14 g of diflunisal (Dolobid, a NSAID), 3 propoxyphene-acetaminophen tablets, and ethanol. Although salicylate ingestion was specifically denied, toxicology screening revealed markedly elevated salicylate levels (176 mg/dL, 100 mg/dL, 41 mg/dL at 4 1/2, 10 and 24 hours postingestion). Blood ethanol level was 450 mg/dL. There was no respiratory alkalosis, metabolic acidosis, or increased anion gap to suggest salicylate toxicity. The patient recovered fully. Comparison testing of the salicylate assay technique used in the case (TDx fluorescence polarization immunoassay) and another commonly used technique (Trinder colorimetric assay) revealed marked cross-reactivity between salicylate and diflunisal. Samples of known diflunisal concentration were tested using the TDx salicylate assay. Percent cross-reactivity [(reported salicylate concentration/actual diflunisal concentration) x 100] was found to be 130 to 152.8% over the concentration range tested. Cross-reactivity between diflunisal and salicylate using the Trinder colorimetric assay was 20 to 52.5% over the concentration range tested. Diflunisal is not metabolized to salicylate and thus this cross-reactivity represents a significant drug-laboratory interaction. Salicylate levels measured by these methods appear to be unreliable when diflunisal is present.