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Evaluation of Cross‐Reactivity of Urinary Digoxin‐like Substance in Different Radioimmunoassays

For the accuracy of routine monitoring of digoxin and digitoxin it seems important to get information on the cross-reactivity of endogenous digitalis-like substances (EDLS). To obtain EDLS, urine was passed on Sep-Pak columns and eluted in fractions by increasing concentrations of acetonitrile. Dilution series of two fractions were subjected to radioimmunoassay (RIA) with respect to digoxin- and digitoxin-like activity, using commercial kits from New England Nuclear, Farmos Diagnostics, and Diagnostic Products Corporation. Cross-reactivity and the degree of parallelism between dilution curves and standard curves varied markedly between the procedures. Recovery studies showed that the presence of EDLS, even at concentrations below the limit of determination of the respective assay, can influence the recovery of digoxin and digitoxin. When higher concentrations of EDLS were present, the combined effects of EDLS and drugs were not always additive. This again stresses the need for any RIA to be carefully characterized to minimize important sources of errors. Required prerequisites are detailed and highly specific information on specificity and the influence of endogenous interfering substances is given. To warrant reliable measurements of digoxin, it is important to identify the cross-reactive material known as EDLS.