Improving the specificity of digoxin immunoassays.

The overall reliability of measuring digoxin in serum improved significantly with the discovery and application of immunoassays. However, because of the low concentration of digoxin being measured, its narrow therapeutic range in serum, and the presence of endogenous digoxin-like immunoreactive factors (DLIF), developing assays for measuring digoxin still pose formidable challenges. In this presentation, recent developments in the characterization of DLIF from bovine adrenal cortex and human serum are described. Data accumulated to date suggest there is one principal endogenous molecular factor (DLIF) in humans that cross-reacts with anti-digoxin antibodies. This factor exists at sufficiently high concentrations in some patients to interfere with measurements of digoxin by most digoxin immunoassays. All digoxin immunoassays should be tested to interference from this endogenous factor. Various techniques for reducing DLIF cross-reactivity are reviewed. The isolation and purification of DLIF now provides new approaches for selecting specific anti-digoxin antibodies used in developing more accurate digoxin immunoassays.