Interference of Oleandrin and Oleandrigenin in Digitoxin Immunoassays

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Abstract
Toxicity from ingestion of the oleander plant is common. Oleandrin, the oleander glycoside, has structural similarity to cardiac glycoside digoxin and is known to cross react with various digoxin immunoassays. The authors studied the cross reactivity of oleandrin and its deglycosylated congener oleandrigenin with a fluorescence polarization immunoassay for digitoxin and compared their results with a new chemiluminescent assay for digitoxin on the Automated Chemiluminescent System (ACS:180 Plus) from Chiron Diagnostics. Even though the chemiluminescent assay has been reported to be comparable with the fluorescence polarization assay among normal patient population, oleandrin and oleandrigenin showed very high cross reactivities with the fluorescence polarization immunoassay and minimal cross reactivity with the new chemiluminescent assay. When the authors supplemented a serum specimen containing no digitoxin with 50 µg/ml of oleandrin, the fluorescence polarization assay recorded a value of 535.7 ng/ml of digitoxin equivalent, whereas the new chemiluminescent assay recorded a value of 10.3 ng/ml of digitoxin equivalent. The cross reactivity of oleandrigenin with the fluorescence polarization immunoassay for digitoxin was significantly lower than oleandrin. The presence of oleandrin also falsely elevated total digitoxin level in a specimen supplemented with digitoxin and oleandrin. The authors also measured free digitoxin concentration by the fluorescence polarization immunoassay in the ultrafiltrate of serum supplemented with digitoxin and oleandrin. Because digitoxin and oleandrin are bound strongly to protein, monitoring free digitoxin concentration by the fluorescence polarization immunoassay instead of total digitoxin concentration does not eliminate oleandrin interference. The authors conclude that fluorescence polarization immunoassay for digitoxin has a high cross reactivity with oleandrin and can falsely elevate digitoxin concentration in the presence of oleandrin, whereas the new chemiluminescent assay for digitoxin is almost free from interferences from oleandrin.