Cross reactivity of digitoxin in radioimmunoassay and enzyme-linked immunoassay for digoxin in plasma.

(Clinical Assays,DMslon ofTravenolLaboratories, Inc., Cambridge,MA 02139).b Duplicate assays. ity of the antisera used in the numerous kit procedures for digoxin. Does the digoxin come from metabolites or only from cross reactivity with digitoxin? To answer this question, we assayed digitoxin standards in the range of the previous concentrations. The digitoxin-free plasma used to prepare the digitoxin standards was also tested and the apparent digoxin (0.35 nmol/L) due to nonspecific binding was subtracted from results for each digitoxin standard. The results (Table 2) show values very similar to those of Table 1, with a mean percentage cross reactivity of 2.55%. This confirms the cross reaction with unchanged digitoxin and a (>12.46) very low rate of digoxin appearance Mean cross 2.32% 40.05% during the metabolism step. reactivi’ a However, two other studies report ‘ $ errors caused by anomalous metabolites. Two hospitalized patients for toxic cardiac symptoms under digitoxin medication gave normal values for ________________________________ digitoxin (15 and 6.5 nmol/L), but toxic values for digoxin (4A and 2.75 nmol/L, respectively). These digoxin . concentrations are produced from digitoxin by a particular metabolic pattern and are very different from those described by Muller et al., who did not compare their results with the digitoxin standard test to determine the nature of interferences. In any case, we think that it isdifficult to estimate the amount of digoxin due to metabolites of digitoxin (0.2 or 0.3 nmol/L) because of the limitation of the main quality criteria for RIA procedures. We conclude that the amount of digitoxin that might bind to the digoxin antibodies in different kit procedures is very variable and depends greatly on the cross reaction of unchanged digitoxin. This discrepancy and the variable cross reactions between methods used to measure the two cardiotonics must be considered, to avoid great errors in clinical interpretation.