Variability among commercially available digoxin radioimmunoassay kits in cross reactivity to dihydrodigoxin

We evaluated four commercially available 125I-digoxin radioimmunoassay kits with regard to their ability to cross react with the digoxin metabolite dehydrodigoxin. We prepared dihydrodigoxin serum samples in digoxin-free serum over the concentration range 0.4 to 5.0 microgram/liter and assayed them with each kit according to the manufacturer's instructions. The metabolite was able to displace the 125I-labeled digoxin derivative from the antibody supplied with all four kits. However, the extent of the cross reactivity depended on the kit, ranging from essentially zero to a high degree of interference. Dihydrodigoxin is the only metabolite of digoxin to have been quantitiated in human serum, and may comprise up to 30% of total glycosides. Over the clinical and therapeutic range of serum digoxin concentrations, enough dihydrodigoxin can be produced to interfere in the determination of serum digoxin concentrations by this method. We suggest that laboratories evaluate their specific kit with regard to cross reactivity to this metabolite.