Rapid detection of convallatoxin using five digoxin immunoassays

Abstract

Context. Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion. Objective. We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses, and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin. Materials and methods. Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro. Results. Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab. Conclusion. Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.

Keywords:

• Convallotoxin
• Lily of the valley
• Oleandrin
• Digoxin
• Digoxin immunoassays

Acknowledgments

We appreciate the advice of Herbert Malkus, and assistance of Maria Galanakis, Florecita Santos and Jennifer Trick in running the digoxin assays.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

Suzanne Ward and BTG Pharmaceuticals provided the DigiFab digoxin immune Fab. This study was funded by the American Academy of Clinical Toxicology Lampe-Kunkel Award and a Connecticut College of Emergency Physicians Resident Research Grant SLF is supported by NIH 2T32HL007974-11.