Analytical quantification of the plant specific cardiac glycosides in biological fluids in a rare case of yellow oleander (Cascabela thevetia) self-poisoning in Italy

Yellow oleander contains digoxin-like cardiac glycosides that frequently cause intoxications in Sri Lanka and India. To date, though, no exposure has been analytically confirmed and quantitative determination of the plant specific glycosides in human biological fluids was never performed. We report an unusual case of self-poisoning in a young female in Italy who ingested 9 crushed seeds of Cascabela thevetia and was admitted to the emergency room with a 2nd degree atrio-ventricular block at the ECG. The case was managed with activated charcoal, repeated doses of anti-digoxin immune Fab and supportive care. A transient thrombocytopenia developed and resolved within a few days. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry was used for the determination and quantification of thevetin A, thevetin B and peruvoside in plasma and urine. Thevetin A and thevetin B, two of the primary glycosides in the seeds, were not present in any of the samples, while detectable levels of the metabolite peruvoside were found in all biological samples on day 1 and 3. Digitoxigenin, the aglycone of thevetin B, was also identified using a semi-untargeted analysis. This is the first report of a quantitative determination of cardiac glycosides of yellow oleander in blood and urine. The finding may support very early administration of activated charcoal to possibly prevent further formation of secondary, and possibly more potent, glycosides and limit toxicity.