RESUMO
Ivabradine is a bradycardic drug used worldwide in the treatment of chronic stable angina and chronic heart failure. We presented here a case of a 61-year-old woman who was admitted to emergency department for overdose. She presented with drowsiness, bradycardia (45bpm) and a low blood pressure (116/21mmHg). She died ten hours after admission from multiple organ failure. Ivabradine was quantified in different matrices sampled during autopsy using a method on LC-MS/MS (TSQ Vantage Thermo Fisher Scientific®), after a double liquid-liquid extraction with a mixture of hexane/ethyl acetate (1/1; v/v) and then chloroform/isopropanol (80/20; v/v). Chromatographic separation was achieved using a Hypersyl gold PFP column (200×2.1mm, 1.9µm) and an acetonitrile/formiate 2mM, 0.1% formic acid buffer gradient. Method was fully validated on whole blood. The mean overall recovery was 90%. Linearity was validated in the 5-500ng/mL range, with intra and inter-day precision lower than 14.3%. The ivabradine concentration found in patient post-mortem blood was 1210ng/mL. Ivabradine was also quantified in different viscera like lung (2910ng/g), kidney (1510ng/g), liver (1050ng/g), heart (900ng/g), and brain (110ng/g). The vitreous humor concentration was 760ng/mL. Pregabalin and zopiclone were also found in blood at 50µg/mL and 206ng/mL, respectively. This case seems to be the first report of a fatal intoxication involving ivabradine and the first published concentrations in organs.