Fatal, Intentional Overdose of Ranolazine: Post-Mortem Distribution of Parent Drug and its Major Metabolite

Ranolazine is a selective inhibitor of the late inward sodium current, approved for the treatment of chronic angina. Here, a case of a possibly suicidal death due to acute ranolazine overdosing is reported. A 41-year-old woman was found unconscious by her son and was urgently admitted to the intensive care unit. She had ingested an unknown amount of ranolazine tablets. Seventeen hours after admission, the patient died. An autopsy was performed 4 days postmortem. A routine screening analysis for drugs of abuse and medicinal drugs performed by liquid chromatography (LC)–ion trap mass spectrometry (MS) on autopsy samples of biological fluids did not detect any relevant presence of toxicologically relevant compounds, but ranolazine. A quantitative analysis was then carried out by liquid chromatography--triple quadrupole (LC–QqQ) MS in order to quantify ranolazine and its major metabolite o-desmethylranolazine in biological fluids and organs. Ranolazine concentrations in biological fluids were as follows: cardiac blood, 19.5 μg/mL; femoral blood, 12.3 μg/mL; bile, 0.87 μg/mL and vitreous humor, 15.4 μg/mL. For O-desmethylranolazine, the concentrations in cardiac blood, femoral blood, bile and vitreous humor were 10.7, 9.6, 11,103 and 11.4 μg/mL, respectively. The cause of death was attributed to ranolazine overdosing. To the best of our knowledge, this is the first report of a fatality associated with ranolazine, in which the postmortem distribution of ranolazine and its metabolite has been quantitatively assessed. The present study can therefore provide useful information for interpretation of the causes and mechanisms of death in ranolazine-associated fatalities.