QUANTITATION OF INTERFERENCE IN DIGOXIN IMMUNOASSAY IN RENAL, HEPATIC, AND DIABETIC DISEASE

A comparison of the results of a newly developed fluorescence-derivati zation/HPLC method and a commercial immunoassay method (ACA, Dupont) f or the measurement of serum digoxin concentrations in patients indicat es that (1) the results from the ACA method agree well with those from the HPLC method in patients with cardiovascular disease but without r enal, diabetic, and liver disease, (2) serum digoxin concentrations de termined by the ACA method are overestimated in patients with renal, d iabetic, or liver disease, and (3) the steady-state serum concentratio ns of hydrolyzed and reduced metabolites are relatively insignificant in patients receiving digoxin therapy, including patients with renal f ailure, The excellent reproducibility of the HPLC and immunoassay meth ods (coefficient of variation <9.0%), together with the demonstrated s pecificity of the HPLC method with respect to potential interference f rom digoxin metabolites, endogenous digoxin-like immunoactive substanc es, and coadministered drugs and their metabolites, allows quantitatio n of the degree of interference in digoxin immunoassays under actual t herapeutic drug monitoring conditions, Clinically significant interfer ences (0.3 to 1.1 ng/ml) with immunoassay determination were found in the majority of patients in all three diseases studied.